bluuebunny/crossref_metadata_2025 huggingface dataset:
A Spatial Econometric Analysis of Cultural Dimensions, Technology Knowledge and Economic Growth
Authors: Barboza Gustavo A. , Pede Valerien O.
Published: April 2012

Using data from 65 countries over the period 1980–2003, this paper investigates the role that cultural dimensions play in the process of technological change, innovation and adoption and consequently on the steady state level of output per worker and its growth, using spatial econometrics techniques to account for spatial dependence between countries. Initial findings indicate that differences across cultural dimensions act as a leveling effect but not as long run growth determinants. In addition, when controlling for physical and human capital accumulation, culture plays a much smaller role in explaining differences in income per capita than initially thought, with little effect on output per worker growth along the transitional dynamics path. Spatial econometric considerations are relevant in explaining differences across rates of growth of per worker output, but not in terms of steady‐state levels of income.
Has the Program 3×1 for Migrants Contributed to Community Development in Mexico? Evidence from Panel Data of 2000 and 2005
Authors: Kijima Yoko , Gonzalez‐Ramirez Horacio
Published: April 2012

This paper examines how collective remittances contribute to regional development by using the community‐level two‐year panel data for the states of Jalisco and Zacatecas in Mexico, which have received the higher amounts of the budget of the Program 3×1 for Migrants. The results from empirical analyses show that the communities that received this program became better‐off between 2000 and 2005, according to the marginalization level. Further analyses suggest that specifically investment in roads, water supply, and non‐agricultural productive projects by the 3×1 program improved community welfare. The regression results on access to the program show, however, that neither the marginalization level nor the migration level determined the access to the program. This suggests that the 3×1 program was not necessarily targeted at the communities with higher marginalization and migration levels.
Reducing Tariffs According to WTO Accession Rules: The Case of Vietnam
Authors: Fosse Henrik Barslund , Raimondos‐Møller Pascalis
Published: April 2012

When Vietnam joined the World Trade Organization (WTO) in 2007 it was granted an accession period up to 2014. During this period tariffs would have to fall according to the accession agreement. This paper evaluates this 2007–2014 trade liberalization by building an applied general equilibrium model and calibrating it to the Vietnamese data. The model pays careful attention to the fact that Vietnam has many state‐owned enterprises. The model simulations show that the WTO tariff reductions will reduce overall welfare. Moreover, the biggest loss will take place among the poor rural households in Vietnam. This paper proposes other tariff reforms that will both raise overall welfare and reduce income inequality.
Regional Economic Disparity, Financial Disparity, and National Economic Growth: Evidence from China
Authors: Lee Bong‐Soo , Peng Jiangang , Li Guanzheng , He Jing
Published: April 2012

The dynamic relations among national economic growth, economic disparity, and financial disparity in China are examined. Specifically, the focus is on whether economic disparity or financial disparity affects national economic growth. As measures of economic and financial disparity across regions and provinces, the Williamson coefficient of disparity is employed using both regional data (eastern, central, and western) and provincial data (from 31 provinces). Overall, it is found that both provincial financial disparity and, to a lesser degree, economic disparity have a negative effect on national economic growth. In addition, financial disparity appears to be exogenous, suggesting that financial disparity is not influenced by either economic disparity or national economic growth.
China's Outward Direct Investment in Africa
Authors: Cheung Yin‐Wong , de Haan Jakob , Qian Xingwang , Yu Shu
Published: April 2012

The empirical determinants of China's outward direct investment (ODI) in Africa are examined using an officially approved ODI dataset and a relatively new OECD–IMF format ODI dataset. China's ODI is found responding to the canonical economic determinants that include the market seeking motive, the risk factor, and the resources seeking motive. It is also affected by the intensity of trade ties and the presence of China's contracted projects. A host country's natural resources have an impact on China's decision on how much to invest in the country rather than on whether to invest in the country or not. China's drive for Africa's natural resources is mainly a recent phenomenon and, probably, became prominent after the “Going Global” policy adopted in 2002.
Quality Assurance and the Home Market Effect
Authors: Goh Ai‐Ting , Michalski Tomasz K.
Published: April 2012

The home market effect is considered as a distinguishing feature of models of trade with increasing returns to scale in production and imperfect competition. However, some empirical studies found the existence of home market effect even in constant returns to scale industries. This paper builds a model of intra‐industry trade based upon quality assurance and shows the existence of the home market effect without increasing returns in the production technology. This throws into question the rationale of empirical studies attempting to validate the increasing returns model of trade based upon testing the existence of the home market effect.
Product Market Imperfection and the Two‐sector Harris–Todaro Economy
Authors: Choi Jai‐Young , Yu Eden S. H.
Published: April 2012

This paper examines the ramifications of market imperfection for a dual economy in the context of the two‐sector Harris–Todaro model with the agricultural (manufacturing) sector under perfect competition (monopoly). Based on a utility function of constant elasticity of substitution variety, it demonstrates (i) existence of a unique equilibrium at which the consumer price ratio and the producer price ratio are synchronized; (ii) several fundamental properties of the model (crucial to extended research on this subject area); (iii) contrary to an earlier result obtained under an oligopolistic manufacturing sector, trade liberalization for a small economy may be immiserizing.
Importing, Exporting, and Innovation in Developing Countries
Authors: Şeker Murat
Published: April 2012

This study shows the persistent differences in evolution of firms when they are grouped according to their trade orientation as: two‐way traders (both importing and exporting), “exporters‐only”, “importers‐only”, and nontraders. Extending the existing models of firm evolution into an open economy setup by incorporating the importing decision, a simple model is presented and it is empirically shown that: (i) globally engaged firms are larger, more productive, and grow faster than nontraders; (ii) two‐way traders are the fastest growing and most innovative group who are followed by exporter‐only firms; and (iii) estimating the export premium without controlling for import status is likely to overestimate the actual value by capturing the import premium. Robustness of the results is shown by providing evidence from the panel data constructed from the original dataset and controlling for variables that are likely to affect firm evolution.
Technology Adoption, Export Status, and Skill Upgrading: Theory and Evidence
Authors: Bas Maria
Published: April 2012

This paper develops a model of trade that features heterogeneous firms, technology choice and different types of skilled labor in a general equilibrium framework to explain within‐industry increase in the relative demand for skilled workers. Its main contribution is to investigate the impact of firms' export and technology choice decisions on skill upgrading. Only firms in the upper range of the productivity distribution produce for the foreign market using high‐technology. Since this technology is skilled‐biased, exporters that resort to modern technologies are more skill intensive. Empirical evidence is also provided to support the model's main predictions using plant‐level panel data from Chile's manufacturing sector (1990–1999).
Real and Financial Integration in East Asia
Authors: Kim Soyoung , Lee Jong‐Wha
Published: April 2012

This paper examines the real and financial integration of East Asian economies, by comparing the degree of real vs financial and global vs regional integration, before vs after the Asian crisis. First, price and quantity measures such as the size of intra‐ and inter‐regional trade, cross‐border financial assets, stock return correlation, and interest rate differentials are investigated. Second, the structural panel vector autoregression (VAR) model is constructed to analyze macroeconomic consequences of real and financial integration such as cross‐country output and consumption relation. The results suggest that (i) the degree of real integration significantly increased after the crisis, both regionally and globally; (iii) quantity and price measures showed an increased financial integration after the crisis, but the consumption relation did not; (iv) the degree of regional financial integration is smaller than that of global financial integration, based on the consumption relation; and (v) financial integration lags real integration, especially for regional integration.
China Bashing: Does Trade Drive the “Bad” News about China in the USA?
Authors: Ramirez Carlos D. , Rong Rong
Published: April 2012

A monthly index of “bad” news about China as reported in the USA from January 1990 to December 2008 is developed in this paper. “Bad” is defined as news touching on the following issues: human rights, Tibet, child labor, democracy, and repression. Using this bad news index, this paper documents a peculiar finding: 3–4 months after a trade deficit shock to the US–China bilateral trade balance, the frequency of bad news published about China by US media outlets rises sharply, then dies off slowly. Statistical analysis reveals that the likelihood that this finding is just a coincidence is relatively small—about 1%. In addition, this paper finds a robust association between the annual number of Congressional hearings on China and the US–China bilateral trade deficit. These results suggest that “China bashing” may be endogenous to fluctuations in the US–China bilateral trade balance.
How Does Foreign Direct Investment Really Affect Developing Countries' Growth?
Authors: Herzer Dierk
Published: April 2012

Two main contributions to literature on foreign direct investment (FDI) and economic growth are made in this paper. First, the paper examines the effect of FDI on economic growth for 44 developing countries using heterogeneous panel cointegration techniques that are robust to omitted variables and endogenous regressors. The main result is that FDI has, on average, a negative effect on growth in developing countries, but there are large differences in the effect across countries. Second, a general‐to‐specific model‐selection approach is used to systematically search for country‐specific factors explaining the cross‐country differences in the growth effects of FDI. The results suggest that the cross‐country heterogeneity in the growth effect of FDI can be explained mainly by cross‐country differences in freedom from government intervention, business freedom, FDI volatility, and primary export dependence.
Does Type of Education Affect Political Participation? Results from a Panel Survey of Swedish Adolescents
Authors: Persson Mikael
Published: April 2012

In several countries it is apparent that individuals with academic gymnasium (upper‐secondary) education show significantly higher levels of political participation than individuals with vocational education. However, previous research on this issue draws exclusively on one‐shot cross‐sectional data. This article utilizes a Swedish panel survey to gauge whether there is a direct causal link between type of education and political participation. Results demonstrate that differences in political participation are already present when students enter different types of education. The analyses show no significant effects of education; instead results support the education‐as‐a‐proxy view: pre‐adult factors predict political participation as well as educational choice.
PERSISTENCE OF REGIONAL UNEMPLOYMENT: APPLICATION OF A SPATIAL FILTERING APPROACH TO LOCAL LABOR MARKETS IN GERMANY*
Authors: Patuelli Roberto , Schanne Norbert , Griffith Daniel A. , Nijkamp Peter
Published: April 2012

ABSTRACT The geographical distribution and persistence of regional/local unemployment rates in heterogeneous economies (such as Germany) have been, in recent years, the subject of various theoretical and empirical studies. Several researchers have shown an interest in analyzing the dynamic adjustment processes of unemployment and the average degree of dependence of the current unemployment rates or gross domestic product from the ones observed in the past. In this paper, we present a new econometric approach to the study of regional unemployment persistence, in order to account for spatial heterogeneity and/or spatial autocorrelation in both the levels and the dynamics of unemployment. First, we propose an econometric procedure suggesting the use of spatial filtering techniques as a substitute for fixed effects in a panel estimation framework. The spatial filter computed here is a proxy for spatially distributed region‐specific information (e.g., the endowment of natural resources, or the size of the “home market”) that is usually incorporated in the fixed effects coefficients. The advantages of our proposed procedure are that the spatial filter, by incorporating region‐specific information that generates spatial autocorrelation, frees up degrees of freedom, simultaneously corrects for time‐stable spatial autocorrelation in the residuals, and provides insights about the spatial patterns in regional adjustment processes. We present several experiments in order to investigate the spatial pattern of the heterogeneous autoregressive coefficients estimated for unemployment data for German NUTS‐3 regions. We find widely heterogeneous but generally high persistence in regional unemployment rates.
MOSTLY POINTLESS SPATIAL ECONOMETRICS?*
Authors: Gibbons Stephen , Overman Henry G.
Published: April 2012

ABSTRACT We argue that identification problems bedevil applied spatial economic research. Spatial econometrics usually solves these problems by deriving estimators assuming that functional forms are known and by using model comparison techniques to let the data choose between competing specifications. We argue that in many situations of interest this achieves, at best, only very weak identification. Worse, in many cases, such an approach will be uninformative about the causal economic processes at work, rendering much applied spatial econometric research “pointless,” unless the main aim is description of the data. We advocate an alternative approach based on the “experimentalist paradigm” which puts issues of identification and causality at center stage.
THE EFFECT OF LAND‐USE CONTROLS ON THE SPATIAL SIZE OF U.S. URBANIZED AREAS*
Authors: Geshkov Marin V. , DeSalvo Joseph S.
Published: April 2012

ABSTRACT On a sample of U.S. urbanized areas in 2000, we test theoretical hypotheses of the effect of land‐use controls on the spatial size of urban areas. We find that minimum lot‐size zoning and maximum FAR restrictions expand the urban area, while maximum lot‐size zoning, urban growth boundaries, minimum square footage limits, maximum building permit restrictions, minimum person per room controls, and impact fees contract the urban area. All of these findings are consistent with theoretical predictions although the effect of urban growth boundaries and minimum square footage limits are not statistically significant.
EXPLAINING THE VARIATION IN THE EMPIRICAL ESTIMATES OF ACADEMIC KNOWLEDGE SPILLOVERS*
Authors: Ghinamo Mauro L.
Published: April 2012

ABSTRACT This paper presents a meta‐regression analysis of the empirical studies exploring the relationship between academic knowledge spillovers and regional innovation. The results of the literature are found to depend on country effects, the level of geographical aggregation employed, the method of measuring innovative output, the use of industry‐level data, and on the sectoral composition of the sample. Endogeneity, sample selection, and agglomeration forces are further elements that explain the findings on this issue but only weak evidence, after controlling for publication bias, supports the existence of a genuine spillover effect of university research on regional innovation.
POPULATION DISPERSION VS. CONCENTRATION IN A TWO‐REGION MIGRATION MODEL WITH ENDOGENOUS NATURAL AMENITIES*
Authors: Chen Yong , Irwin Elena G. , Jayaprakash Ciriyam
Published: April 2012

ABSTRACT Contrary to the predictions of the basic spatial equilibrium model, the long‐run distribution of population across rural U.S. counties with high‐valued natural amenities has become relatively more concentrated versus dispersed. We provide an explanation by developing a two‐region model with mobile labor, production externalities and endogenous natural amenities. We find that strong preferences for natural amenities generally foster population dispersion. However, such preferences can also lead to population concentration when ecological degradation is low and man‐made capital is a relatively scarce input into natural amenity production. Investments that enhance natural amenities are found to reduce the divergence between the steady state and optimal outcomes.
DUOPOLISTIC HIRING AND SALES COMPETITION—A THEORETICAL AND EXPERIMENTAL ANALYSIS
Authors: Berninghaus Siegfried K. , Güth Werner , Hoppe Christian , Paul Christian
Published: April 2012

Two firms compete in selling as well as hiring, where sales levels depend on the hired workforce. There are two types of workers, mobile and immobile, differing in effort costs, and two workers of each type. The principals offer contracts to all workers, who then select an employer. Finally, the workers determine production levels and profits. Our experimental results show: vanishing cost differences between mobile and immobile workers induce monopolistic hiring but low profits. In contrast, large cost differences result in higher profits and allow for various hiring constellations such as one firm hiring only low‐cost workers.
Living Up to Lenin: Leadership Culture and the Spanish Communist Party, 1920–1939*
Authors: REES TIM
Published: April 2012

In its quest to spread the Bolshevik revolution around the world, the Communist International (Comintern) sought to create a strong leadership culture among communist parties. This article examines the experience of the Spanish Communist Party (PCE). It shifts the focus away from a traditional concern with the individual or collective characters and capabilities of leaders, towards an analysis of the everyday characteristics and behaviours required of leaders, what they signified and the degree to which the PCE conformed in practice to ‘Leninist’ archetypes. While there was an active acceptance within the PCE of the need to emulate the Bolshevik example, the specifically Spanish cultural and political environment in which party leaders operated also exerted a powerful influence. Consequently, the PCE only ever partially conformed to the Comintern's leadership doctrines, and its leaders inevitably fell short of Bolshevik ideals.
Scene‐context effect in visual memory is independent of retention interval1
Authors: INOUE KAZUYA , TAKEDA YUJI
Published: April 2012

The context of a natural scene can facilitate memory for embedded objects. It has been reported that such scene‐context effects can be lost in the flicker paradigm, which alternatively presents a picture, followed by a modified version of the picture after a brief interval. Using a follow‐the‐dot paradigm which instills serial attending, determinants of the scene‐context effect are examined by varying both scene‐context (normal, jumbled) and the retention interval (short, long) between cued and target objects. In this paradigm, a dot cue was sequentially presented on 12 different objects of a scene, then the memory for one of the cued objects was tested. This paradigm requires holding information about multiple objects in memory at once. Retention intervals were varied by manipulating the serial position of the dot on a target object. The results showed that the retention interval did not influence the scene‐context effect. Potential mechanisms for the scene‐context effect are discussed.
Detection of a change in photorealism1
Authors: SEYAMA JUNICHIRO , NAGAYAMA RUTH S
Published: April 2012

The perceived degree of photorealism is interpreted as reflecting the artificialness or naturalness of images. Natural images (real‐scene photographs) are images with high degrees of naturalness, while artificial images (e.g., paintings) are images with low degrees of naturalness. Alternatively, natural images are images with low degrees of artificialness, while artificial images are images with high degrees of artificialness. We attempted to disambiguate these two interpretations of the perception of photorealism by using a change‐blindness paradigm. Participants observed an image sequence showing a gradual transformation from a natural image to an artificial image or vice versa, and reported changes they noticed. More participants reported noticing changes in photorealism for the natural‐to‐artificial transformations than for the opposite transformations. This asymmetry indicates that disappearing naturalness was detected more readily than emerging naturalness, or alternatively, emerging artificialness was detected more readily than disappearing artificialness. The results for the control conditions showed that the emergence of visual information was detected more readily than the disappearance. These results suggest that the perception of photorealism should be considered as the perception of artificialness.
The effects of social memories in autobiographical elaboration on incidental memory
Authors: TOYOTA HIROSHI
Published: April 2012

The present study compared the effects of social memories with those of nonsocial memories on incidental memory. The participants were presented target words on two occasions, and each time they were asked to think of a past episode associated with them in the orienting task, followed by an unexpected free‐recall test. The results showed that the targets that were associated with social memories, episodes including any person, were recalled more often than those with nonsocial memories. Also, the spacing effect was observed only for the recall of target words associated with social memories. These results were interpreted as showing that the inclusion of any particular person in an episode makes an episode itself more distinctive as an effective cue in autobiographical elaboration.
Abundance and exploitation of loggerhead turtles nesting in Boa Vista island, Cape Verde: the only substantial rookery in the eastern Atlantic
Authors: Marco A. , Abella E. , Liria‐Loza A. , Martins S. , López O. , Jiménez‐Bordón S. , Medina M. , Oujo C. , Gaona P. , Godley B. J. , López‐Jurado L. F.
Published: April 2012

The main nesting area for loggerhead turtles in the eastern Atlantic is in the Cape Verde Islands, largely restricted to the island of Boa Vista. Extensive monitoring demonstrated a globally significant population for the species despite a sustained high level of anthropogenic take of nesting females for local consumption. Through an extensive stratified monitoring program across the island in the seasons 2007–2009, we estimated a total of 13 955, 12 028 and 19 950 clutches in the 3 years, respectively. These values indicate that the mean number of nesting females averaged 3700. Considering that a female breed, on average, every 2.4 years, we estimate that the overall number of adult females in the population during these three seasons was 8900. These levels are much higher than those suggested in previous studies which were more constrained in spatial coverage. Our findings indicate that Cape Verde hosts the third largest nesting aggregation for this species in the world after the south‐eastern US and Oman, with some sites having a particularly high density of nests, facilitating targeted monitoring and conservation. Consumption of sea turtle meat is a traditional practice in Cape Verde that continues despite national sea turtle protection laws. We estimated that 36, 18 and 5% of nesting females were harvested in the 3 years of the study, respectively. Increasing beach protection and monitoring, ongoing educational programs and cooperative projects with local communities are urgently needed to further safeguard the only major loggerhead nesting aggregation in the eastern Atlantic.
Interspecific divergence of ionoregulatory physiology in killifish: insight into adaptation and speciation
Authors: Berdan E. L. , Fuller R. C.
Published: April 2012

Adaptation to salinity is potentially a critical driving force of speciation in fishes. Here, we tested for differences in ion/osmoregulatory gene expression between two species of killifish Lucania goodei and L. parva that differ in salinity tolerance. Expression patterns of several genes encoding ion transport proteins were quantified for animals taken directly from populations that varied in salinity, as well as animals from a salinity transfer experiment. We found that L. parva, a euryhaline species, expressed higher levels of the genes involved in saltwater ion/osmoregulatory regulation than its stenohaline counterpart L. goodei (Na+/K+‐ATPase 1a and 1b, Na+‐K+‐2Cl‐ cotransporter 1 and glucocorticoid receptor) when exposed to a change in salinity in the laboratory. However, both species expressed similar levels for two of the three genes involved in freshwater osmoregulation (14‐3‐3a and V‐type H+‐ATPase). Surprisingly, we found little evidence for differential plasticity between L. parva and L. goodei in our salinity transfer experiment. Lucania parva expressed high levels of genes involved in both freshwater and saltwater ion/osmoregulation, while L. goodei only expressed high levels of genes involved in freshwater osmoregulation. These results indicate that L. parva may increase their transcript levels of osmoregulatory genes when faced with any type of salinity challenge. Thus, changes in ion/osmoregulatory physiology may be occurring post‐transcriptionally via differential RNA processing or enzyme activity. These findings provide unique insight into the ion/osmoregulatory physiology that underlies species and population differences in salinity tolerance.
Ancient microbial activity recorded in fracture fillings from granitic rocks (Äspö Hard Rock Laboratory, Sweden)
Authors: HEIM C. , LAUSMAA J. , SJÖVALL P. , TOPORSKI J. , DIEING T. , SIMON K. , HANSEN B. T. , KRONZ A. , ARP G. , REITNER J. , THIEL V.
Published: April 2012

Fracture minerals within the 1.8‐Ga‐old Äspö Diorite (Sweden) were investigated for fossil traces of subterranean microbial activity. To track the potential organic and inorganic biosignatures, an approach combining complementary analytical techniques of high lateral resolution was applied to drill core material obtained at −450 m depth in the Äspö Hard Rock Laboratory. This approach included polarization microscopy, time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS), confocal Raman microscopy, electron microprobe (EMP) and laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS). The fracture mineral succession, consisting of fluorite and low‐temperature calcite, showed a thin (20–100 μm), dark amorphous layer lining the boundary between the two phases. Microscopic investigations of the amorphous layer revealed corrosion marks and, in places, branched tubular structures within the fluorite. Geochemical analysis showed significant accumulations of Si, Al, Mg, Fe and the light rare earth elements (REE) in the amorphous layer. In the same area, ToF‐SIMS imaging revealed abundant, partly functionalized organic moieties, for example, CxHy+, CxHyN+, CxHyO+. The presence of such functionalized organic compounds was corroborated by Raman imaging showing bands characteristic of C‐C, C‐N and C‐O bonds. According to its organic nature and the abundance of relatively unstable N‐ and O‐ heterocompounds, the organic‐rich amorphous layer is interpreted to represent the remains of a microbial biofilm that established much later than the initial cooling of the Precambrian host rock. Indeed, δ13C, δ18O and 87Sr/86Sr isotope data of the fracture minerals and the host rock point to an association with a fracture reactivation event in the most recent geological past.
HOW TO MEASURE LIVING STANDARDS AND PRODUCTIVITY
Authors: OULTON NICHOLAS
Published: April 2012

I set out a general algorithm for calculating true cost‐of‐living indices when demand is not homothetic and when the number of products may be large. The non‐homothetic case is the important one empirically (Engel's Law). The algorithm can be applied in both time series and cross section. It can also be used to estimate true producer price indices and Total Factor Productivity in the presence of input‐biased economies of scale and technical change. The basic idea is to calculate a chain index of prices but with actual budget (cost) shares replaced by compensated shares, i.e. what the shares would have been if consumers (firms) faced actual prices but their utility (output) were held constant at some reference level. The compensated shares can be derived econometrically from the same data as are required for the construction of conventional index numbers. The algorithm is illustrated by applying it to estimating true PPPs for 141 countries and 100 products within household consumption, using data from the World Bank's latest International Comparison Program.
Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic beta‐cell area and function in Zucker diabetic fatty rats
Authors: Feigh M , Andreassen KV , Neutzsky‐Wulff AV , Petersen ST , Hansen C , Bay‐Jensen AC , Henriksen JE , Beck‐Nielsen H , Christiansen C , Henriksen K , Karsdal MA
Published: April 2012

BACKGROUND AND PURPOSE

Oral salmon calcitonin (sCT), a dual‐action amylin and calcitonin receptor agonist, improved glucose homeostasis in diet‐induced obese rats. Here, we have evaluated the anti‐diabetic efficacy of oral sCT using parameters of glycaemic control and beta‐cell morphology in male Zucker diabetic fatty (ZDF) rats, a model of type 2 diabetes.

EXPERIMENTAL APPROACH

Male ZDF rats were treated with oral sCT (0.5, 1.0 or 2 mg·kg−1) or oral vehicle twice daily from age 8 to 18 weeks. Zucker lean rats served as control group. Fasting and non‐fasted blood glucose, glycosylated haemoglobin (HbA1c) and levels of pancreas and incretin hormones were determined. Oral glucose tolerance test and i.p. glucose tolerance test were compared, and beta‐cell area and function were evaluated.

KEY RESULTS

Oral sCT treatment dose‐dependently attenuated fasting and non‐fasted hyperglycaemia during the intervention period. At the end of the study period, oral sCT treatment by dose decreased diabetic hyperglycaemia by ∼9 mM and reduced HbA1c levels by 1.7%. Furthermore, a pronounced reduction in glucose excursions was dose‐dependently observed for oral sCT treatment during oral glucose tolerance test. In addition, oral sCT treatment sustained hyperinsulinaemia and attenuated hyperglucagonaemia and hypersecretion of total glucagon‐like peptide‐1 predominantly in the basal state. Lastly, oral sCT treatment dose‐dependently improved pancreatic beta‐cell function and beta‐cell area at study end.

CONCLUSIONS AND IMPLICATIONS

Oral sCT attenuated diabetic hyperglycaemia in male ZDF rats by improving postprandial glycaemic control, exerting an insulinotropic and glucagonostatic action in the basal state and by preserving pancreatic beta‐cell function and beta‐cell area.
RAGE: a new frontier in chronic airways disease
Authors: Sukkar Maria B , Ullah Md Ashik , Gan Wan Jun , Wark Peter AB , Chung Kian Fan , Hughes J Margaret , Armour Carol L , Phipps Simon
Published: April 2012

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous inflammatory disorders of the respiratory tract characterized by airflow obstruction. It is now clear that the environmental factors that drive airway pathology in asthma and COPD, including allergens, viruses, ozone and cigarette smoke, activate innate immune receptors known as pattern‐recognition receptors, either directly or indirectly by causing the release of endogenous ligands. Thus, there is now intense research activity focused around understanding the mechanisms by which pattern‐recognition receptors sustain the airway inflammatory response, and how these mechanisms might be targeted therapeutically. One pattern‐recognition receptor that has recently come to attention in chronic airways disease is the receptor for advanced glycation end products (RAGE). RAGE is a member of the immunoglobulin superfamily of cell surface receptors that recognizes pathogen‐ and host‐derived endogenous ligands to initiate the immune response to tissue injury, infection and inflammation. Although the role of RAGE in lung physiology and pathophysiology is not well understood, recent genome‐wide association studies have linked RAGE gene polymorphisms with airflow obstruction. In addition, accumulating data from animal and clinical investigations reveal increased expression of RAGE and its ligands, together with reduced expression of soluble RAGE, an endogenous inhibitor of RAGE signalling, in chronic airways disease. In this review, we discuss recent studies of the ligand–RAGE axis in asthma and COPD, highlight important areas for future research and discuss how this axis might potentially be harnessed for therapeutic benefit in these conditions.
Activation of endothelial and epithelial KCa2.3 calcium‐activated potassium channels by NS309 relaxes human small pulmonary arteries and bronchioles
Authors: Kroigaard Christel , Dalsgaard Thomas , Nielsen Gorm , Laursen Britt E , Pilegaard Hans , Köhler Ralf , Simonsen Ulf
Published: April 2012

BACKGROUND AND PURPOSE

Small (KCa2) and intermediate (KCa3.1) conductance calcium‐activated potassium channels (KCa) may contribute to both epithelium‐ and endothelium‐dependent relaxations, but this has not been established in human pulmonary arteries and bronchioles. Therefore, we investigated the expression of KCa2.3 and KCa3.1 channels, and hypothesized that activation of these channels would produce relaxation of human bronchioles and pulmonary arteries.

EXPERIMENTAL APPROACH

Channel expression and functional studies were conducted in human isolated small pulmonary arteries and bronchioles. KCa2 and KCa3.1 currents were examined in human small airways epithelial (HSAEpi) cells by whole‐cell patch clamp techniques.

RESULTS

While KCa2.3 expression was similar, KCa3.1 protein was more highly expressed in pulmonary arteries than bronchioles. Immunoreactive KCa2.3 and KCa3.1 proteins were found in both endothelium and epithelium. KCa currents were present in HSAEpi cells and sensitive to the KCa2.3 blocker UCL1684 and the KCa3.1 blocker TRAM‐34. In pulmonary arteries contracted by U46619 and in bronchioles contracted by histamine, the KCa2.3/ KCa3.1 activator, NS309, induced concentration‐dependent relaxations. NS309 was equally potent in relaxing pulmonary arteries, but less potent in bronchioles, than salbutamol. NS309 relaxations were blocked by the KCa2 channel blocker apamin, while the KCa3.1 channel blocker, charybdotoxin failed to reduce relaxation to NS309 (0.01–1 µM).

CONCLUSIONS AND IMPLICATIONS

KCa2.3 and KCa3.1 channels are expressed in the endothelium of human pulmonary arteries and epithelium of bronchioles. KCa2.3 channels contributed to endo‐ and epithelium‐dependent relaxations suggesting that these channels are potential targets for treatment of pulmonary hypertension and chronic obstructive pulmonary disease.
Contractile, but not endothelial, dysfunction in early inflammatory arthritis: a possible role for matrix metalloproteinase‐9
Authors: Reynolds SL , Williams AS , Williams H , Smale S , Stephenson HJ , Amos N , George SJ , O'Donnell VB , Lang D
Published: April 2012

BACKGROUND AND PURPOSE Excess morbidity/mortality in rheumatoid arthritis (RA) is associated with increased incidence of cardiovascular disease. In this ‘proof‐of‐concept’ study, vascular function was characterized in the murine collagen‐induced arthritis (mCIA) model, the benchmark choice for evaluation of the pathological processes and assessment of new therapies.

EXPERIMENTAL APPROACH Mice in the very early stages of arthritis development [and appropriate naïve (non‐immunized) age‐matched controls] were used in the study. Blood pressure was measured using tail cuff plethysmography. Vascular function in rings of isolated aorta was studied with isometric tension myography. Levels of NO metabolites (NOx), MMP‐9 protein and IL‐1β in plasma and MMP‐9 protein in aortic homogenates were quantified.

KEY RESULTS Impaired vascular contractile responses in arthritis were unaffected by ex vivo inhibition of NOS (endothelial/neuronal and inducible) or COX activities. Endothelium‐dependent and ‐independent relaxation, plasma NOx and blood pressure were unaffected by arthritis. Plasma and aortic homogenate MMP‐9 protein levels were increased significantly in arthritis. Incubation of aortic tissues from naïve control animals with exogenous MMP‐9 impaired subsequent contractile responses, mirroring that observed in arthritis. A role for IL‐1β in perpetuating contractile dysfunction and increasing aortic MMP‐9 was excluded.

CONCLUSIONS AND IMPLICATIONS These data identify for the first time a relationship between early arthritis and contractile dysfunction and a possible role for MMP‐9 therein, in the absence of overt endothelial dysfunction or increased NO production. As such, MMP‐9 may constitute a significant target for early intervention in RA patients with a view to decreasing risk of cardiovascular disease.
Selective block of KATP channels: why the anti‐diabetic sulphonylureas and rosiglitazone have more in common than we thought
Authors: Dart Caroline
Published: April 2012

Rosiglitazone, the thiazolidinedione class anti‐diabetic withdrawn from Europe in 2010 amid reports of adverse cardiovascular effects, is revealed by Yu et al. in this issue of the British Journal of Pharmacology to be a selective blocker of ATP‐sensitive potassium (KATP) channels. This seems little cause for excitement given that the closure of pancreatic KATP channels is integral to insulin secretion; and sulphonylureas, which inhibit KATP channels, are widely used to treat type II diabetes. However, rosiglitazone, whose primary targets are nuclear transcription factors that regulate genes involved in lipid metabolism, blocks KATP channels by a novel mechanism different to that of the sulphonylureas and has a worrying preference for blood flow–regulating vascular KATP channels. Identification of a new molecule that modulates KATP channel gating will not only tell us more about how these complex metabolic sensors work but also raises questions as to whether rosiglitazone suppresses the cardiovascular system's ability to cope with metabolic stress – a claim that has dogged the sulphonylureas for many years.

LINKED ARTICLE

This article is a commentary on Yu et al., pp. 26–36 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476‐5381.2012.01934.x
The Strange Case of Dr. Bucaille: Notes for a Re‐examination
Authors: Bigliardi Stefano
Published: April 2012

The present essay focuses on the figure of Maurice Bucaille and on his contribution to the discourse on Islam and science. Its purpose is twofold. First of all, it aims to provide the reader with a concise map of the ideas of the French author, reconstructing their core and their interrelations. Furthermore, it aims to question what I define as “the apparent naivety” of Bucaille's work, a reason why he can sometimes be too easily dismissed, by pinpointing a number of original features of his intellectual activity. My argument is that Bucaille deserves more attention for two good reasons: firstly, because of the influence that he de facto exerts on Muslim societies, secondly, because of some highly specific characteristics of his discourse. Such features not only distinguish his contribution from analogous ones, but also give rise to interpretative questions, which have as yet been either overlooked or unsatisfactorily addressed. Closely connected to this thesis is the idea that Bucaille's work constitutes a good starting point for a discussion amongst scholars of different disciplines and from different cultural backgrounds. The first section reconstructs Bucaille's life and works. The second section focuses on his method and ideas regarding science. The third section is devoted to Bucaille's conclusions following his study of the Bible and the Qur'an, and therefore deals more closely with the core of his ideas. The fourth section covers Bucaille's complementary criticism of the theory of evolution. In the fifth section I examine the possible reasons behind the scant scholarly attention concerning Bucaille. In the final section I propose an interpretative model of Bucaille's figure conceived as a system of concentric spheres and I raise, for each one of them, several questions, which have so far been, in my view, insufficiently investigated, thus setting an agenda for further scholarly work.
Current limits and future challenges in the management of renal dysfunction in patients with cirrhosis: report from the International Club of Ascites
Authors: Angeli Paolo , Sanyal Arun , Moller Soren , Alessandria Carlo , Gadano Adrian , Kim Ray , Sarin Shiv K. , Bernardi Mauro
Published: April 2012

Advanced cirrhosis is often complicated by a multi organ failure syndrome which involves many different organs besides the liver. The high morbidity and mortality secondary to this clinical setting is often related to renal dysfunction, either alone or, more frequently, in combination with other organ dysfunction. A clear defintion of renal dysfunction, an accurate differential diagnostic process of its different phenotypes as well as of full understanding of its pathophysiological mechanisms are crucial to the development of strategies for the management of this complication. This article is based either on the more recent knowledge on renal dysfunction in advanced cirrhosis or current opinions among the members of the International Club of Ascites (ICA) on the management of this complication, obtained through a survey and discussed during the EASL‐ICA Joint Meeting in Berlin in March 2011. It reviews critically our current knowledge and it outlines future perspectives, on the management of renal dysfunction in patients with cirrhosis.
A Case of Tinea Versicolor of the Eyelids
Authors: Huang William W. , Tharp Michael D.
Published: April 2012

Abstract:  Tinea versicolor is a commonly encountered superficial fungal infection often presenting on the chest and back with hyperpigmented or hypopigmented scaly macules and patches. We report an unusual and rare presentation of tinea versicolor affecting only the eyelids.
Asymmetric cortical surface area and morphology changes in mesial temporal lobe epilepsy with hippocampal sclerosis
Authors: Alhusaini Saud , Doherty Colin P. , Palaniyappan Lena , Scanlon Cathy , Maguire Sinead , Brennan Paul , Delanty Norman , Fitzsimons Mary , Cavalleri Gianpiero L.
Published: April 2012

Purpose:  To date, magnetic resonance imaging (MRI)–based studies of the cerebral cortex in mesial temporal lobe epilepsy (MTLE) have focused primarily on investigating cortical volume and thickness. However, volume is a composite of surface area and thickness, each reflecting distinct neurobiologic and genetic processes. The goal of this study was to investigate cerebral cortex (1) surface area, (2) surface geometric distortion, and (3) thickness in MTLE with hippocampal sclerosis (HS).

Methods:  Seventy patients with “sporadic” unilateral MTLE + HS and 40 healthy controls underwent T1‐weighted MRI. Processing MR images using an automated cortical surface reconstruction method (FreeSurfer), we quantified cortical surface area, surface geometric distortion (metric distortion), and thickness at each vertex across the entire cortex. Differences between patients and controls were determined using generalized linear models. Separate linear regression models were employed to assess the relationship between cortical surface area and hippocampal volume as well as a series of important clinical features of the condition.

Key Findings:  We detected an asymmetric reduction in cortical surface area, predominantly in ipsilateral mesial and anterior temporal lobe subregions, of patients with MTLE + HS. Changes in surface geometric features were also evident and closely mirrored surface area patterns. In contrast, cortical thinning appeared dispersed across the cortex bilaterally. The regression models revealed that ipsilateral hippocampal volume was a significant predictor of temporal lobe surface area changes.

Significance:  Our findings indicate that contraction in surface area, rather than cortical thinning, explains ipsilateral mesial and anterior temporal lobe atrophy in patients with MTLE with HS. Furthermore, the alterations in surface geometry indicate folding abnormality involving the same regions. Cortical surface changes may represent sequelae of the disease or deviant cortical development.
Choline Supplementation and DNA Methylation in the Hippocampus and Prefrontal Cortex of Rats Exposed to Alcohol During Development
Authors: Otero Nicha K. H. , Thomas Jennifer D. , Saski Christopher A. , Xia Xiaoxia , Kelly Sandra J.
Published: April 2012

Background

Some of the most frequent deficits seen in children with fetal alcohol spectrum disorders (FASD) and in animal models of FASD are spatial memory impairments and impaired executive functioning, which are likely related to alcohol‐induced alterations of the hippocampus and prefrontal cortex (PFC), respectively. Choline, a nutrient supplement, has been shown in a rat model to ameliorate some of alcohol's teratogenic effects, and this effect may be mediated through choline's effects on DNA methylation.

Methods

Alcohol was given by intragastric intubation to rat pups during the neonatal period (postnatal days 2 to 10) (ET group), which is equivalent to the third trimester in humans and a period of heightened vulnerability of the brain to alcohol exposure. Control groups included an intubated control group given the intubation procedure without alcohol (IC) and a nontreated control group (NC). Choline or saline was administered subcutaneously to each subject from postnatal days 2 to 20. On postnatal day 21, the brains of the subjects were removed and assayed for global DNA methylation patterning as measured by chemiluminescence using the cpGlobal assay in both the hippocampal region and PFC.

Results

Alcohol exposure caused hypermethylation in the hippocampus and PFC, which was significantly reduced after choline supplementation. In contrast, control animals showed increases in DNA methylation in both regions after choline supplementation, suggesting that choline supplementation has different effects depending upon the initial state of the brain.

Conclusions

This study is the first to show changes in global DNA methylation of the hippocampal region and PFC after neonatal alcohol exposure. Choline supplementation impacts global DNA methylation in these 2 brain regions in alcohol‐exposed and control animals in a differential manner. The current findings suggest that both alcohol and choline have substantial impact on the epigenome in the PFC and hippocampus, and future studies will be needed to describe which gene families are impacted in such a way that function of the nervous system is changed.