bluuebunny/crossref_metadata_2025 huggingface dataset:
The Triggers or Precipitants of the Acute Migraine Attack
Authors: Kelman L
Published: March 2007

The aim of this study was to evaluate and define the triggers of the acute migraine attack. Patients rated triggers on a 0-3 scale for the average headache. Demographics, prodrome, aura, headache characteristics, postdrome, medication responsiveness, acute and chronic disability, sleep characteristics and social and personal characteristics were also recorded. One thousand two hundred and seven International Classification of Headache Disorders-2 (1.1-1.2, and 1.5.1) patients were evaluated, of whom 75.9% reported triggers (40.4% infrequently, 26.7% frequently and 8.8% very frequently). The trigger frequencies were stress (79.7%), hormones in women (65.1%), not eating (57.3%), weather (53.2%), sleep disturbance (49.8%), perfume or odour (43.7%), neck pain (38.4%), light(s) (38.1%), alcohol (37.8%), smoke (35.7%), sleeping late (32.0%), heat (30.3%), food (26.9%), exercise (22.1%) and sexual activity (5.2%). Triggers were more likely to be associated with a more florid acute migraine attack. Differences were seen between women and men, aura and no aura, episodic and chronic migraine, and between migraine and probable migraine.
Type 2 transglutaminase differentially modulates striatal cell death in the presence of wild type or mutant huntingtin
Authors: Ruan Qingmin , Quintanilla Rodrigo A. , Johnson Gail V. W.
Published: March 2007

Huntington’s disease (HD), which is caused by an expanded polyglutamine tract in huntingtin (htt), is characterized by extensive loss of striatal neurons. The dysregulation of type 2 transglutaminase (TG2) has been proposed to contribute to the pathogenesis in HD as TG2 is up‐regulated in HD brain and knocking out TG2 in mouse models of HD ameliorates the disease process. To understand the role of TG2 in the pathogenesis of HD, immortalized striatal cells established from mice in which mutant htt with a polyglutamine stretch of 111 Gln had been knocked‐in and wild type (WT) littermates, were stably transfected with human TG2 in a tetracycline inducible vector. Overexpression of TG2 in the WT striatal cells resulted in significantly greater cell death under basal conditions as well as in response to thapsigargin treatment, which causes increased intracellular calcium concentrations. Furthermore, in WT striatal cells TG2 overexpression potentiated mitochondrial membrane depolarization, intracellular reactive oxygen species production, and apoptotic cell death in response to thapsigargin. In contrast, in mutant striatal cells, TG2 overexpression did not increase cell death, nor did it potentiate thapsigargin‐induced mitochondrial membrane depolarization or intracellular reactive oxygen species production. Instead, TG2 overexpression in mutant striatal cells attenuated the thapsigargin‐activated apoptosis. Whenin situtransglutaminase activity was quantitatively analyzed in these cell lines, we found that in response to thapsigargin treatment TG2 was activated in WT, but not mutant striatal cells. These data suggest that mutant htt alters the activation of TG2 in response to certain stimuli and therefore differentially modulates how TG2 contributes to cell death processes.
Effects of the monomeric, oligomeric, and fibrillar Aβ42 peptides on the proliferation and differentiation of adult neural stem cells from subventricular zone
Authors: Heo Chaejeong , Chang Keun‐A , Choi Hee Soon , Kim Hye‐Sun , Kim Seonghan , Liew Hyunjeong , Kim Jeong a , Yu Eunah , Ma Jie , Suh Yoo‐Hun
Published: March 2007

The incidence of amyloid plaques, composed mainly of β‐amyloid peptides (Aβ), does not correlate well with the severity of neurodegeneration in patients with Alzheimer’s disease (AD). The effects of Aβ42 on neurons or neural stem cells (NSCs) in terms of the aggregated form remain controversial. We prepared three forms of oligomeric, fibrillar, and monomeric Aβ42 peptides and investigated their effects on the proliferation and neural differentiation of adult NSCs, according to the degree of aggregation or concentration. A low micromolar concentration (1 μmol/L) of oligomeric Aβ42 increased the proliferation of adult NSCs remarkably in a neurosphere assay. It also enhanced the neuronal differentiation of adult NSCs and their ability to migrate. These results provide us with valuable information regarding the effects of Aβ42 on NSCs in the brains of patients with AD.
Toll‐like receptor (TLR)‐2 and TLR‐4 regulate inflammation, gliosis, and myelin sparing after spinal cord injury
Authors: Kigerl Kristina A. , Lai Wenmin , Rivest Serge , Hart Ronald P. , Satoskar Abhay R. , Popovich Phillip G.
Published: March 2007

Activation of macrophages via toll‐like receptors (TLRs) is important for inflammation and host defense against pathogens. Recent data suggest that non‐pathogenic molecules released by trauma also can trigger inflammation via TLR2 and TLR4. Here, we tested whether TLRs are regulated after sterile spinal cord injury (SCI) and examined their effects on functional and anatomical recovery. We show that mRNA for TLR1, 2, 4, 5, and 7 are increased after SCI as are molecules associated with TLR signaling (e.g. MyD88, NFκB). The significance of in vivo TLR2 and TLR4 signaling was evident in SCI TLR4 mutant (C3H/HeJ) and TLR2 knockout (TLR2−/−) mice. In C3H/HeJ mice, sustained locomotor deficits were observed relative to SCI wild‐type control mice and were associated with increased demyelination, astrogliosis, and macrophage activation. These changes were preceded by reduced intraspinal expression of interleukin‐1β mRNA. In TLR2−/− mice, locomotor recovery also was impaired relative to SCI wild‐type controls and novel patterns of myelin pathology existed within ventromedial white matter – an area important for overground locomotion. Together, these data suggest that in the absence of pathogens, TLR2 and TLR4 are important for coordinating post‐injury sequelae and perhaps in regulating inflammation and gliosis after SCI.
Heat‐shock protein 105 interacts with and suppresses aggregation of mutant Cu/Zn superoxide dismutase: clues to a possible strategy for treating ALS
Authors: Yamashita Hirofumi , Kawamata Jun , Okawa Katsuya , Kanki Rie , Nakamizo Tomoki , Hatayama Takumi , Yamanaka Koji , Takahashi Ryosuke , Shimohama Shun
Published: March 2007

A dominant mutation in the gene for copper‐zinc superoxide dismutase (SOD1) is the most frequent cause of the inherited form of amyotrophic lateral sclerosis. Mutant SOD1 provokes progressive degeneration of motor neurons by an unidentified acquired toxicity. Exploiting both affinity purification and mass spectrometry, we identified a novel interaction between heat‐shock protein 105 (Hsp105) and mutant SOD1. We detected this interaction both in spinal cord extracts of mutant SOD1G93A transgenic mice and in cultured neuroblastoma cells. Expression of Hsp105, which is found in mouse motor neurons, was depressed in the spinal cords of SOD1G93A mice as disease progressed, while levels of expression of two other heat‐shock proteins, Hsp70 and Hsp27, were elevated. Moreover, Hsp105 suppressed the formation of mutant SOD1‐containing aggregates in cultured cells. These results suggest that techniques that raise levels of Hsp105 might be promising tools for alleviation of the mutant SOD1 toxicity.
Sphingolipid signalling and liver diseases
Authors: Marí Montserrat , Fernández‐Checa José C.
Published: March 2007

Sphingolipids (SLs) comprise a class of lipids with important structural functions and increasing relevance in cellular signalling. In particular, ceramide has attracted considerable attention owing to its role as a second messenger modulating several cell functions such as proliferation, gene expression, differentiation, cell cycle arrest and cell death. Increasing evidence documents the role of SLs in stress and death ligand‐induced hepatocellular death, which contributes to the progression of several liver diseases including steatohepatitis, ischaemia‐reperfusion liver injury or hepatocarcinogenesis. Furthermore, recent data indicate that the accumulation of SLs in specific cell subcompartments, characteristic of many sphingolipidoses, contributes to the hepatic dysfunctions that accompany these inherited diseases. Hence, the regulation of the cell biology and metabolism of SLs may open up a novel therapeutic avenue in the treatment of liver diseases.
The Myth of “Security Moms” and “NASCAR Dads”: Parenthood, Political Stereotypes, and the 2004 Election*
Authors: Elder Laurel , Greene Steven
Published: March 2007

Objective. The objective of this article is to explore the impact of being a parent on political views and to test the accuracy of the “Security Mom” and “NASCAR Dad” labels that were pervasively applied in the context of the 2004 presidential election.

Methods. The methods we employed consist of using data primarily from the 2004 National Election Study to determine whether parents differ from nonparents in terms of their political attitudes on a wide range of issues. We argue that parenthood affects women and men differently, so we analyze the sexes separately.

Results. Mothers have important political distinctions from women without children, mostly in the case of social welfare issues. They do not, however, appear to be “Security Moms” in the post‐9/11 world. As for fathers, for the most part it makes little sense to talk about dads as a distinct voting bloc, as in very few cases do their political attitudes differ from men without children.

Conclusions. The media's use of the labels “NASCAR Dad” and Security Mom” promoted an inaccurate understanding of the political preferences of parents. Beyond debunking these media myths, our results provide one of the first comprehensive looks at the impact of parenthood on political attitudes, an overlooked area in the adult socialization literature.
Branded: The Economic Geographies of Streets Named in Honor of Reverend Dr. Martin Luther King, Jr.*
Authors: Mitchelson Matthew L. , Alderman Derek H. , Popke E. Jeffrey
Published: March 2007

Objectives. We investigate the economic geographies of streets named for Reverend Dr. Martin Luther King, Jr. (MLK Streets), which are an increasingly common means by which various community members across the United States are attempting to commemorate the slain civil rights leader. It is our intent to characterize these negatively “branded” spaces in order to challenge some of the common perceptions about them and inform current and future MLK Street naming debates.

Methods. We statistically analyze nonresidential establishments located on streets named for King in terms of scale (as measured by annual sales and employment) and industrial classification. To our knowledge, this is the first such analysis conducted at the national level.

Results. Establishments located on MLK Streets do not systematically exhibit economic marginality. Establishments located on these streets do systematically exhibit unique local functions and industrial composition.

Conclusion. In the absence of empirically‐driven research, the negative stereotypes that surround MLK Streets have gone unchallenged and are proliferating. The research reported here calls into question a number of these stereotypes and should inform the public, city councils, and other local policymakers, who are increasingly being faced with contentious MLK Street naming debates.
Does Higher Socioeconomic Status Increase Contact Between Minorities and Whites? An Examination of Interracial Romantic Relationships Among Adolescents*
Authors: Wang Hongyu , Kao Grace
Published: March 2007

Objectives. We examine how socioeconomic status of white, black, Hispanic, and Asian adolescents affects their likelihood of dating across racial lines and the racial characteristics of their romantic partners.

Methods. We analyze data nationally representative sample of adolescents in 1994–1995 using logistic regression models.

Results. Socioeconomic status has little effect on whether adolescents choose an interracial partner except in the case of Hispanics. However, higher socioeconomic status blacks and Asians who interracially date are more likely to have white partners than their SES counterparts.

Conclusion. Although social class does not increase the odds of interracial contact, it does increase contact with whites compared to other groups for blacks and Asians.
Psychoeconomic Approaches to the Study of Hostile Attitudes Toward Minority Groups: A Study Among Israeli Jews*
Authors: Halperin Eran , Pedahzur Ami , Canetti‐Nisim Daphna
Published: March 2007

Objective. We aspired to reexamine the well‐established assumption according to which low socioeconomic status, as a comprehensive concept, leads to prejudice and hostile attitudes toward minorities. Hence, we focused on examining the differential effect of each component of SES on one of the most important behavioral aspects of hostile attitudes—social distance. Just as importantly, we examined the assumption according to which threat perception mediates the influence of SES factors on those attitudes.

Methods. In field research that took place in Israel in May 2003, attitudes of 383 participants toward three distinct minority groups were tested according to their ascription to four different “socioeconomic status” groups.

Results. Contrary to most previous findings, we found that employment status and relative income have very little influence on social distance toward minorities. On the other hand, we found that level of education has a significant effect on social distance and that this effect is mostly mediated by the perception of cultural and economic threat.

Conclusions. The subjective perception of threat was found to be a critical mediating “junction” in the evolutionary process of the influence of socioeconomic factors on hostile attitudes. Therefore, only specific SES components that influence the perception of threat have an effect on hostile attitudes toward minorities.
Email Effects on the Structure of Local Associations: A Social Network Analysis*
Authors: Weare Christopher , Loges William E. , Oztas Nail
Published: March 2007

Objectives. This article explores the impact of email on the network structure of small, voluntary associations. By focusing on the density and centralization of associations, we illuminate how the Internet affects their cohesiveness and democratic character.

Methods. Based on network data collected from 41 community‐based associations that are comparable on a variety of factors known to influence network structure, we employ multiple regression techniques to explore the impact of increased email use on group‐ and individual‐level network measures.

Results. We find that the technological nature of email as well as the background, interests, and intentions of its users interact to influence density and centralization. Individuals employ electronic mail differently from other communication modes such as phone and face‐to‐face communication. Network density increases, and network centralization either increases or decreases, depending on the distribution of email use in the association.

Conclusions. These effects on associational structure are likely to have significant long‐run impacts on the cohesion, efficacy, and democratic character of voluntary associations.
Predicting the Comparative Strengths of National Football Teams*
Authors: Gelade Garry A. , Dobson Paul
Published: March 2007

Objectives. The aim of this study was to identify the chief social and economic factors predicting the strength of national Association Football (soccer) teams.

Methods. A theoretical model was developed to establish an appropriate functional form for the relationship between team strength and the number of individuals available for selection. OLS regression was used to predict the performance ratings of 201 national teams.

Results. The results showed that the strength of a nation's football team depends on the number of men who regularly play football, the length of its football tradition, the wealth of its population, the percentage of expatriate players in the national team, and climatic conditions. These factors explain 70 percent of the variance in international team ratings.

Conclusions. Many of the factors that determine team strength are structural and cannot be manipulated by policymakers. Nations could, however, strengthen their teams by encouraging wider participation in the sport. Poorer nations could develop stronger teams by encouraging their best players to play professional club football abroad, although this might have negative consequences for domestic football.
Fatigue of Lead Zirconate Titanate Ceramics. I: Unipolar and DC Loading
Authors: Balke Nina , Lupascu Doru C. , Granzow Torsten , Rödel Jürgen
Published: March 2007

In actuator applications, a degradation of the ferroelectric material occurs both under unipolar cycling as well as DC loads. The developing material state is characterized by measurements of large and small signal unipolar as well as bipolar hysteresis loops. While the unipolar loops indicate a small decrease in strain and polarization amplitudes, the bipolar loops unveil the development of an offset field, an offset polarization, and an asymmetry in the hysteresis of strain and dielectric constant. A mechanism for unipolar fatigue is suggested to explain the observed changes in material properties with cyclic loading.
Fatigue of Lead Zirconate Titanate Ceramics II: Sesquipolar Loading
Authors: Balke Nina , Lupascu Doru C. , Granzow Torsten , Rödel Jürgen
Published: March 2007

Piezoelectric actuators generally are driven with unipolar electric load cycles. Although the obtainable strain is increased by small excursions into the negative field regime, this type of load cycle is rarely considered, as its long‐time reliability has been questioned. Here, we investigate the degradation of lead zirconate titanate during cycling between high positive and low negative electric fields. Measurements of the large and small signal parameters are used to quantify changes of the material. The fatigue behavior shifts from one best described with existing models of unipolar fatigue to bipolar‐like fatigue with increasing field amplitude.
Transmission Electron Microscopy and Nuclear Magnetic Resonance Studies of Geopolymers for Radioactive Waste Immobilization
Authors: Blackford Mark G. , Hanna John V. , Pike Kevin J. , Vance Eric R. , Perera Dan S.
Published: March 2007

Transmission electron microscopy of a geopolymer phase, derived from metakaolin and alkaline silicate solutions and having nominal Na/Al and Si/Al molar ratios of 1 and 2, respectively, showed it to be amorphous on the ∼1 nm scale after curing at 40°C. In samples containing 5 wt% Cs or Sr, Cs inhabited the amorphous phase, whereas Sr was incorporated only partly, being preferentially partitioned to crystalline SrCO3. Heating progressively to dewater the material had little effect on the overall structure for temperatures up to 500°C. From solid‐state nuclear magnetic resonance in material cured at near‐ambient temperatures, Cs, like Na, was found to be basically associated with pore water, but with significant linkage to the aluminosilicate framework, more so than for Na. Subsequent heating to 300°C increased the linkage of Cs and Na to the framework.
Resistance to Thermal Shock and to Oxidation of Metal Diborides–SiC Ceramics for Aerospace Application
Authors: Monteverde Frédéric , Scatteia Luigi
Published: March 2007

Two SiC‐containing metal diborides materials, classified in the ultra‐high‐temperature ceramics (UHTCs) group, were fabricated by hot‐pressing. SiC, sinterability apart, promoted resistance to oxidation of the diboride matrices. Both the compositions, oxidized in air at 1450°C for 1200 min, had mass gains lower than 5 mg/cm2. Slight deviations from parabolic oxidation kinetics were seen. The resistance to thermal shock (TSR) was studied through the method of the retained flexure strength after water quenching (20°C of bath temperature). Experimental data showed that the (ZrB2+HfB2)–SiC and the ZrB2–SiC materials retained more than 70% of their initial mean flexure strength for thermal quenchs not exceeding 475° and 385°C, respectively. Certain key TSR properties (i.e., fracture strength and toughness, elastic modulus, and thermal expansion coefficient) are very similar for the two compositions. The observed superior critical thermal shock of the (ZrB2+HfB2)–SiC composite was explained in terms of more favorable heat transfer parameters conditions that induce less severe thermal gradients across the specimens of small dimensions (i.e., bars 25 mm × 2.5 mm × 2 mm) during the quench down in water. The experimental TSRs are expected to approach the calculated R values (196° and 218°C for ZrB2+HfB2–SiC and ZrB2–SiC, respectively) as the specimen size increases.
High‐Load Friction Behavior of a Hinge Bearing Based on a Carbon/Silicon Carbide Composite
Authors: Zhang Yani , Zhang Litong , Cheng Laifei , Xu Yongdong
Published: March 2007

Two‐dimensional carbon fiber‐reinforced silicon carbide matrix (C/SiC) composites used for hinge bearing were prepared by chemical vapor infiltration. The testing and results of unlubricated friction behavior of hinge bearing under high‐load transmitting motion was investigated. The effects of load on friction behavior between different sliding couple were analyzed. Finally, worn surfaces and debris were observed by scanning electron microscopy to study the wear mechanism. A constant friction coefficient between self‐mated C/SiC composites of 0.68 was obtained on increasing load up to about 5800 N. Excellent wear resistance and load‐carrying ability was demonstrated by low wear and especially small deformation.
Effects of ambient acidity on chemosensory learning: an example of an environmental constraint on acquired predator recognition in wild juvenile Atlantic salmon (Salmo salar)
Authors: Leduc A. O. H. C. , Roh E. , Breau C. , Brown G. E.
Published: March 2007

Abstract – In many prey fish species, learning the identity of novel predators may be facilitated when novel predator cues and an aversive stimulus are presented together. Damage‐released chemical alarm cues are typically released from the skin of prey individuals following mechanical damage and are known to mediate the learned recognition of novel predators. While such chemically mediated acquired predator recognition can provide increased survival benefits to prey, environmental constraints impeding learning may exist. For example, in several fish species the ability to detect chemical alarm cues is impaired in under acidic conditions and as such, inhibits this chemically mediated learning. In this experiment, we studied in two streams of different mean acidity level (pHc. 6.0 and 7.0), to assess if wild juvenile Atlantic salmon (Salmo salar) had the ability to acquire the recognition of a novel lemon essence odour when paired with conspecific chemical alarm cues. Our results demonstrate that under acidic conditions, no learned recognition of the novel odour occurred. In neutral conditions, however, salmon recognised the novel odour as a predation threat. This result suggests that ambient acidity creates an environmental constraint on chemically mediated learned recognition of a novel cue.
Frequency, composition and stability of associations among individual largemouth bass (Micropterus salmoides) at diel, daily and seasonal scales
Authors: Hasler C. T. , Hanson K. C. , Cooke S. J. , Tinline R. , Suski C. D. , Niezgoda G. , Phelan F. J. S. , Philipp D. P.
Published: March 2007

Abstract –  A whole‐lake acoustic telemetry observatory situated in eastern Ontario was used to continuously monitor the three‐dimensional position of 20 largemouth bass (Micropterus salmoides) over a 120‐h period during the winter and a separate 120‐h period during the early spring. These data were used to evaluate the frequency and stability of associations among fish to provide an understanding of seasonal aggregations and the sociobiology of largemouth bass. The temporal and spatial proximity of each fish relative to the other 19 individuals was assessed and, based on our definition of spatial/temporal proximity (i.e., two fish having an average hourly position <2 m apart), associations were shown to vary among fish, as well as diurnally, daily and seasonally. Associations during the winter were found to be more stable and involved fewer fish than associations during the spring. Of those fish that formed pair aggregations during the winter and spring study periods, male–female pairs occurred more often than male–male and female–female pairs. Our analysis also demonstrated that associations occurred primarily during daylight hours, suggesting that fish may use visual cues to form these aggregations.
Growth‐independent effects of a fluctuating thermal regime on the life‐history traits of the Japanese medaka (Oryzias latipes)
Authors: Dhillon R. S. , Fox M. G.
Published: March 2007

Abstract –  Temperature fluctuation has been shown to affect somatic growth rates and metabolic functions of fish, but little is known about the effects of fluctuating temperatures on life‐history traits. We examined these effects on female Japanese medaka (Oryzias latipes) reared from hatch to maturity at two mean temperatures (27 and 30 °C) with diel temperatures either held constant or allowed to fluctuate ±5 °C. Feeding regimes were manipulated to equilibrate medaka growth rates in all treatments. Age and length at maturity decreased as a result of thermal fluctuation, whereas there was no effect of temperature fluctuation on the proportion of fish attaining maturity or on the number of eggs produced by a mature female. We hypothesise that short‐term high temperatures associated with temperature fluctuation decreases development time, whereas reduced energy conversion efficiency at higher temperatures does not allow for increased egg production.
Genetic diversity of longtail macaques (Macaca fascicularis) on the island of Mauritius: an assessment of nuclear and mitochondrial DNA polymorphisms
Authors: Kawamoto Y. , Kawamoto S. , Matsubayashi K. , Nozawa K. , Watanabe T. , Stanley M.‐A. , Perwitasari‐Farajallah D.
Published: March 2007

Background  Individuals from an introduced population of longtail macaques on Mauritius have been extensively used in recent research. This population has low MHC gene diversity, and is thus regarded as a valuable resource for research.

Methods  We investigated the genetic diversity of this population using multiple molecular markers located in mitochondrial DNA and microsatellite DNA loci on the autosomes and the Y chromosome. We tested samples from 82 individuals taken from seven study sites.

Results and conclusions  We found this population to be panmictic, with a low degree of genetic variability. On the basis of an mtDNA phylogeny, we inferred that these macaques’ ancestors originated from Java in Asia. Weak gametic disequilibrium was observed, suggesting decay of non‐random associations between genomic genes at the time of founding. The results suggest that macaques bred in Mauritius are valuable as model animals for biomedical research because of their genetic homogeneity.
Epidemiology of periodontal status in dentate adults in France, 2002–2003
Authors: Bourgeois D. , Bouchard P. , Mattout C.
Published: March 2007

Background and Objective:  Few recent nationwide studies of the periodontal landscape in European countries have been developed from the point of view of attachment loss and pocket depth. Decision makers are not always in a position to estimate the burden of periodontal disease. The purpose of this study was to investigate the prevalence and the oral distribution of periodontal status among dentate adults in the general population of France.

Material and Methods:  In 2002–2003, a National Periodontal and Systemic Examination Survey was organized to a stratified quota sample of 2144 adults, aged 35–64 years, nationwide. Participants with six or more teeth were selected from the Health Examination Centers of the National Health Insurance. Measurement of periodontal health was assessed by clinical attachment level and probing depth.

Results:  A total of 95.40% and 82.23% of adults were found to have clinical attachment loss and periodontal pockets, respectively. Population prevalence estimates indicated that loss of attachment ≥ 5 mm is 46.68% and probing depth (> 5 mm) is 10.21%. However, clinical attachment loss of ≥ 5 mm occurred in only 0.88 sites in an individual. Periodontal depth pocket generalized forms were as follows: 78% slight, 18% moderate and 4% severe. Multiple logistic regression analyses showed significant differences of attachment loss values between types of tooth (molar, incisors, canines, or premolars).

Conclusion:  Based on the International Classification of Periodontal Diseases, ≈ 50% of adults in France may suffer from a severe attachment loss problem. Periodontal pockets are an uncommon condition in France. Significant differences in the prevalence of loss of attachment and probing depth with respect to location of attack have implications in the purchase and development of screening and treatment services.
Coordination of three and four Cu(I) to the α− and β‐domain of vertebrate Zn‐metallothionein‐1, respectively, induces significant structural changes
Authors: Dolderer Benedikt , Echner Hartmut , Beck Alexander , Hartmann Hans‐Jürgen , Weser Ulrich , Luchinat Claudio , Del Bianco Cristina
Published: March 2007

Vertebrate metallothioneins are found to contain Zn(II) and variable amounts of Cu(I), in vivo, and are believed to be important for d10‐metal control. To date, structural information is available for the Zn(II) and Cd(II) forms, but not for the Cu(I) or mixed metal forms. Cu(I) binding to metallothionein‐1 has been investigated by circular dichroism, luminescence and 1H NMR using two synthetic fragments representing the α‐ and the β‐domain. The 1H NMR data and thus the structures of Zn4α metallothionein (MT)‐1 and Zn3βMT‐1 were essentially the same as those already published for the corresponding domains of native Cd7MT‐1. Cu(I) titration of the Zn(II)‐reconstituted domains provided clear evidence of stable polypeptide folds of the three Cu(I)‐containing α‐ and the four Cu(I)‐containing β‐domains. The solution structures of these two species are grossly different from the structures of the starting Zn(II) complexes. Further addition of Cu(I) to the two single domains led to the loss of defined domain structures. Upon mixing of the separately prepared aqueous three and four Cu(I) loaded α‐ and β‐domains, no interaction was seen between the two species. There was neither any indication for a net transfer of Cu(I) between the two domains nor for the formation of one large single Cu(I) cluster involving both domains.
A pilot (real‐life) randomised clinical evaluation of a pain‐relieving foam dressing: (ibuprofen‐foam versus local best practice)
Authors: Sibbald R Gary , Coutts Patricia , Fierheller Marjorie , Woo Kevin
Published: March 2007

The aim of the study was to evaluate a novel foam dressing with continuous low‐level release of ibuprofen (Biatain‐Ibu foam dressing, Coloplast A/S, Humlebaek, Denmark) in persons with leg ulcers compared to local best practice. An open comparative and prospective block‐randomised study of 24 patients was conducted in a Canadian wound clinic. Twelve patients were randomised to ibuprofen–foam and 12 patients to local best practice. The study population consisted of patients with chronic, painful exudating leg ulcers. The patients rated their wound pain intensity at baseline and after the first dressing application. Pain intensity in the morning and evening was rated during a period of 1 week using a numeric box scale (NBS). A t‐test compared the main differences in pain intensity and a five‐point verbal rating scale measured the patients’ pain relief. At the last clinical visit, pain after dressing change was assessed using an NBS. In addition, wound size, percentage of healthy granulation tissue and the presence of peri‐ulcer erythema, were (all) evaluated at inclusion and the end of the study. The nurses and patients both evaluated the relative dressing performance and exudate management at the last study visit. This study demonstrates that the ibuprofen–foam dressing decreased wound pain in patients with leg ulcers compared to best practice. The ibuprofen–foam dressing was associated with: diminished chronic pain between dressing changes, reduced acute pain at dressing change, increased healthy granulation tissue, decreased peri‐wound erythema and excellent exudate handling capacity. It can be concluded from the results of the study that the combination of foam with a continuous low‐dose release of ibuprofen may offer a valuable new therapeutic approach to the reduction of wound pain.
Less pain with Biatain–Ibu: initial findings from a randomised, controlled, double‐blind clinical investigation on painful venous leg ulcers
Authors: Gottrup Finn , Jørgensen Bo , Karlsmark Tonny , Sibbald R Gary , Rimdeika Rytis , Harding Keith , Price Patricia , Venning Vanessa , Vowden Peter , Jünger Michael , Wortmann Stephan , Sulcaite Rita , Vilkevicius Gintaris , Ahokas Terttu‐Liisa , Ettler Karel , Arenbergerova Monika
Published: March 2007

Six out of 10 patients with chronic wounds suffer from persistent wound pain. A multinational and multicentre, randomised, double‐blind clinical investigation of 122 patients compared two moist wound‐healing dressings, a non adhesive foam dressing with ibuprofen (62 patients randomised to Biatain‐Ibu non adhesive, Coloplast A/S) with a non adhesive foam without ibuprofen (60 to Biatain non adhesive).The ibuprofen‐foam was regarded successful, if the pain relief on a 5‐point verbal rating scale was higher than the comparator without compromising safety, including appropriate healing rate. Additional endpoints were change in persistent wound pain between dressing changes and pain at dressing change on days 1–5 and days 43–47. The primary response variable, persistent pain relief, was significantly higher in the ibuprofen‐foam group compared with the comparator on days 1–5, with a quick onset of action (P < 0·05). The patients in the ibuprofen‐foam group had a significant (P < 0·05) higher reduction in the persistent wound pain from baseline (40%) as the comparator (30%). Women reported less pain intensity than men, and pain intensity decreased with increasing age. In addition, pain intensity increased with increasing initial pain intensity and increasing wound size. Wound healing was similar in the ibuprofen‐foam group to that of the comparator group. No difference in adverse events between placebo and local sustained release of low‐dose ibuprofen was observed in this study. This study has demonstrated that the ibuprofen‐foam dressing provided pain relief and reduced pain intensity without compromising healing or other safety parameters. The full report of this study will be published in Wound Repair and Regeneration.
Protection of Geographical Indications in China: Conflicts, Causes and Solutions
Authors: Xiaobing Wang , Kireeva Irina
Published: March 2007

This article provides an example of protection of geographical indications in China and describes how this intellectual property type is protected in China, why protection of this type of intellectual property resulted in adoption of conflicting laws and regulations, what the causes of such a situation were and how it is managed at the present moment. The interest for China may be explained not only by the size of its territory and population but also by its history, tradition and the role played in international trade since China became a World Trade Organization member. At present, China has a dual system for the protection of geographical indications. On the one hand, it protects geographical names as certification and collective trademarks. On the other hand, it recognizes specific products of high quality and offers sui generis protection to the geographical names of such products.
Modulation of expression of Na+/Ca2+ exchanger in heart of rat and mouse under stress
Authors: Hudecova S. , Kubovcakova L. , Kvetnansky R. , Kopacek J. , Pastorekova S. , Novakova M. , Knezl V. , Tarabova B. , Lacinova L. , Sulova Z. , Breier A. , Jurkovicova D. , Krizanova O.
Published: March 2007

Aim:  The Na+/Ca2+ exchanger (NCX) is a major Ca2+ extrusion system in the plasma membrane of cardiomyocytes and an important component participating on the excitation–contraction coupling process in muscle cells. NCX1 isoform is the most abundant in the heart and is known to be changed after development of ischaemia or myocardial infarction. Objective of this study was to investigate the effect of stress factors (immobilization, cold and short‐term hypoxia) on the expression of NCX1, in vivo, in the heart of rat and mouse.

Methods:  We compared gene expression and protein levels of control and stressed animals. The activity of NCX was measured by the whole cell configuration using the patch clamp. We also measured physiological parameters of the heart in physiological conditions and under ischaemia‐reperfusion to compare response of control and stressed hearts.

Results:  We have found that only strong stress stimulus (hypoxia, immobilization) applied repeatedly for several days elevated the NCX1 mRNA level. Cold, which is a weaker stressor that activates mainly sympathoneural, and only marginally adrenomedullary system did not affect the gene expression of NCX1. Thus, from these results it appears that hormones produced by the adrenal medulla (mainly adrenaline) might be involved in this process. To study possible mechanism of the NCX1 regulation by stress, we focused on the possible role of the hypothalamo–pituitary–adrenocortical pathway in the activation of catecholamine synthesis in the adrenal medulla. We have already published that cortisol affects activity, but not the gene expression of NCX1. In this work, we used corticotropin‐releasing hormone (CRH) knockout mice, where secretion of corticosterone and subsequently adrenaline is significantly suppressed. As no increase in NCX1 mRNA was observed in CRH knockout mice due to immobilization stress, we proposed that adrenaline (probably regulated via corticosterone) is involved in the regulation of NCX1 gene expression during stress.

Conclusions:  The gene expression and protein levels of the NCX1 are increased by the strong stress stimuli, e.g. hypoxia, or immobilization stress. The activity of NCX1 is decreased. Based on these results, we assume that the gene expression of NCX is increased as a consequence of suppressed activity of this transport system.
Enhanced β‐adrenergic response in rat papillary muscle by inhibition of inducible nitric oxide synthase after myocardial infarction
Authors: Pinto V. D. , Cutini G. J. S. , Sartório C. L. , Paigel A. S. , Vassallo D. V. , Stefanon I.
Published: March 2007

Aim:  Myocardial infarction (MI) induces a progressive ventricular remodelling leading to a contractility depression. During the acute phase of MI inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production increases in the heart. The aim of this study was to investigate the role of iNOS in the left ventricular contractility at 3 days after MI.

Methods:  Wistar rats were divided into: sham operated (SHAM, n = 23), infarction (INF, n = 18); sham operated plus the iNOS inhibitor, S‐methylisothiourea (SMT) 5 mg kg−1 day−1, i.p. treatment (SHAM‐SMT, n = 26) and infarction plus SMT (INF‐SMT, n = 22). Concentration–response curves for isoprenaline, Ca2+ and frequency–force curve were studied in isolated papillary muscle from left ventricle.

Results:  After 3 days infarct area was similar between groups. SMT treatment reduced the time to peak tension during frequency–force curve in the infarct group (SHAM = 63 ± 3; SHAM‐SMT = 71 ± 3; INF = 90 ± 4; INF‐SMT = 79 ± 4 ms, P < 0.05) and increased the maximal response to isoprenaline (SHAM = 0.93 ± 0.11; SHAM‐SMT = 1.13 ± 0.1; INF =0.84 ± 0.16; INF‐SMT = 1.49 ± 0.15 g mm−2, P < 0.05). The response to Ca2+ was equally reduced in the INF and INF‐SMT groups. SMT treatment did not change the reduced post‐rest potentiation performed by INF group, but attenuated the plasma nitrite and nitrate (NOx) levels in the INF group without any haemodynamic effect.

Conclusion:  These finding suggest that at 3 days after MI the iNOS modulates the isolated papillary muscle response to isoprenaline and its inhibition improves the β‐adrenergic inotropic responses.
Skeletal muscle fatty acid transporter protein expression in type 2 diabetes patients compared with overweight, sedentary men and age‐matched, endurance‐trained cyclists
Authors: Pelsers M. M. A. L. , Tsintzas K. , Boon H. , Jewell K. , Norton L. , Luiken J. J. F. P. , Glatz J. F. C. , Van Loon L. J. C.
Published: March 2007

Aim:  Membrane fatty acid transporters can modulate the balance between fatty acid uptake and subsequent storage and/or oxidation in muscle tissue. As such, skeletal muscle fatty acid transporter protein expression could play an important role in the etiology of insulin resistance and/or type 2 diabetes.

Methods:  In the present study, fatty acid translocase (FAT/CD36), plasma membrane‐bound fatty acid‐binding protein (FABPpm) and fatty acid transport protein 1 (FATP1) mRNA and protein expression were assessed in muscle tissue obtained from 10 sedentary, overweight type 2 diabetes patients (60 ± 2 years), 10 sedentary, weight‐matched normoglycemic controls (60 ± 2 years) and 10 age‐matched, endurance trained cyclists (57 ± 1 years).

Results:  Both FAT/CD36 and FATP1 mRNA and protein expression did not differ between groups. In contrast, FABPpm mRNA and protein expression were approx. 30–40% higher in the trained men compared with the diabetes patients (P < 0.01) and sedentary controls (P < 0.05).

Conclusions:  Skeletal muscle FAT/CD36, FABPpm and FATP1 mRNA and protein expression are not up‐ or downregulated in a sedentary and/or insulin resistant state. In contrast, FABPpm expression is upregulated in the endurance trained state and likely instrumental to allow greater fatty acid oxidation rates.
Increased TFF1 trefoil protein expression in Opisthorchis viverrini‐associated cholangiocarcinoma is important for invasive promotion
Authors: Thuwajit Peti , Chawengrattanachot Watinee , Thuwajit Chanitra , Sripa Banchob , May Felicity E. B. , Westley Bruce R. , Tepsiri Nisana N. , Paupairoj Anucha , Chau‐in Siri
Published: March 2007

Aims:  Cholangiocarcinoma (CCA) is a poor prognosis cancer that presents with metastatic disease. This cancer expresses MUC5AC, a mucin which normally co‐expresses with trefoil factor family 1 (TFF1) protein. TFF1 is a signalling protein that can activate epithelial cell invasion and has been considered as a metastasis stimulating agent. The aim of this study was to determine the co‐expression of TFF1 and MUC5AC in CCA tissues and examine the activity of TFF1 for stimulating the invasive property of CCA cell lines.

Methods:  In this study, TFF1 and MUC5AC were detected in CCA tissues by using immunohistochemistry. The correlations of both proteins expression with clinical data were analyzed. The activity of TFF1 was investigated using an in vitro invasion assay with established CCA cell lines KKU‐100 and KKU‐M213.

Results:  We demonstrated a high level of expression of TFF1 in 91.80% of CCA that is associated with a high level of co‐expression with MUC5AC in 80.33% of cases. In vitro invasion assay showed that both cell lines have similar responses to TFF1 that could act as both a chemokinetic and chemotactic agent. The dose‐response curves were bell‐shaped.

Conclusion:  TFF1 showed co‐expression with MUC5AC in CCA tissues and invasive stimulating activity in vitro. These results may indicate a role for TFF1 in promoting tumor invasion in CCA.
Impaired cytotoxic T lymphocyte inductivity by dendritic cells derived from patients with hepatitis C virus‐positive hepatocellular carcinoma
Authors: Ohno Tomoyoshi , Hirashima Noboru , Orito Etsuro , Hasegawa Izumi , Fujiwara Kei , Itoh Kiyoaki , Ozasa Atsushi , Shinkai Noboru , Tanaka Yasuhito , Kato Takanobu , Ueda Ryuzo , Sakakibara Kenji
Published: March 2007

Aim:  Peptide‐based therapeutic vaccines are being developed. The aim of this study was to determine the feasibility of immunotherapy to hepatitis C virus (HCV)‐positive hepatocellular carcinoma (HCC) by assessing the inductivity of peptide‐specific cytotoxic T lymphocyte (CTL) by dendritic cells.

Methods:  The inductivity of CTL was characterized in six patients with HCV‐positive HCC, and compared to seven healthy volunteers and six patients with chronic HCV hepatitis (control).

Results:  Peptide‐specific CTL was comparably induced in controls, but not induced in any patients with HCC. To characterize this, the cytokine profile and the expression of surface molecules interacting between dendritic and T cells were evaluated. Among the cytokines, production of interferon (IFN)‐γ was found to be impaired and closely related to the results of CTL assays, while the expression of surface molecules showed no significant changes.

Conclusions:  In HCV‐positive HCC patients, CTL inductivity by dendritic cells is impaired. This may be related to the impaired production of IFN‐γ.
Amniotic epithelial cell–derived cholangiocytes in experimental cholestatic ductal hyperplasia
Authors: Moritoki Yuki , Ueno Yoshiyuki , Kanno Noriatsu , Yamagiwa Yoko , Fukushima Koji , Gershwin M. Eric , Shimosegawa Tooru
Published: March 2007

Aim:  Bile duct paucity, ductopenia, is a feature of end‐stage chronic cholangiopathies such as primary biliary cirrhosis. The limited proliferative ability of cholangiocytes after specific injury is thought to be the principal cause of ductopenia, although the detailed mechanisms involved are unclear. It has been reported that human amniotic epithelial cells (AEC) express differentiation markers of hepatic parenchymal cells, suggesting a resemblance of AEC to hepatic progenitor cells. The aim of the present study was to develop a mouse model of experimental cholestasis to assess the capability of mouse AEC to trans‐differentiate into cholangiocytes.

Methods:  Enhanced green fluorescent protein (EGFP)‐transgenic C57BL/6 pregnant female mice were used as the source of AEC. At 11.5 gestational days, 1 × 105 AEC were isolated from EGFP‐transgenic mouse embryos and transferred into C57BL/6 mice. Chronic cholestasis was induced by 0.1%α‐naphthylisothiocyanate (ANIT) feeding immediately after the transfer of AEC. The proliferation of cholangiocytes in the livers was assessed morphologically and immunohistochemically (cytokeratin 7; CK7). The proliferative activity was also quantified immunohistochemically by proliferating cell nuclear antigen (PCNA) protein expression. EGFP of transferred AEC was confirmed by fluorescent laser microscopy and immunofluorescent staining for EGFP. Also, Notch2 and Hes1 expression was evaluated to examine the roles of the differentiation markers in this process.

Results:  Marked proliferation of cholangiocytes was observed in ANIT‐fed mice confirmed by quantitative CK7 (3–4 fold vs control) and PCNA (11–20 fold vs control) staining. EGFP and CK7 double positive cells in interlobular bile ducts were confirmed in the livers of AEC‐transferred recipients. Positivity of EGFP was further confirmed by the immunofluorescent staining for EGFP. Moreover, both Notch2 and Hes1 expression was confirmed in the proliferative bile duct in this model.

Conclusions:  Significant ductular proliferation was observed in ANIT‐fed mice. EGFP‐positive cholangiocytes were confirmed in this chronic cholestasis model. AEC transfer was able to contribute to the repopulating of proliferating cholangiocytes under cholestasis, suggesting AEC might be a candidate cell source for stem cell administration in future clinical applications to re‐model interlobular bile ducts.