bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepcidin treatment in Hfe−/− mice diminishes plasma iron without affecting erythropoiesis
Authors: Morán‐Jiménez María‐Josefa , Méndez Manuel , Santiago Begoña , Rodríguez‐García María‐Elena , Moreno‐Carralero María‐Isabel , Sánchez‐Lucío Ana‐Cristina , Grau Montserrat , Enríquez‐de‐Salamanca Rafael 
Published: April 2010

Eur J Clin Invest 2010; 40 (6): 511–517AbstractBackground  Iron is essential for mammalian metabolism and its cellular concentration is controlled by regulating its acquisition and storage. Haemochromatosis is a condition involving iron overload that is characterised by increased duodenal iron absorption and a progressive accumulation of iron in vital organs. Hepcidin is the main hormone that regulates iron homoestasis and it is secreted by the liver.Materials and methods  We have studied how extended hepcidin administration affects the iron load status, plasma and tissue iron concentration, erythropoiesis and the expression of proteins involved on iron homeostasis in haemochromatotic (Hfe−/−) and wild‐type mice.Results  Hepcidin reverted the high plasma iron concentrations in Hfe−/− mice to normal values. The high concentration of hepatic iron was not altered in the liver of these Hfe−/− mice. Hepcidin administration did not disturb erythropoiesis in either Hfe−/− or wild‐type mice and likewise, hepcidin did not modify the expression of any protein analysed in the liver, duodenum or spleen of Hfe−/− and wild‐type mice. These data confirm that hepcidin administration diminishes plasma iron concentrations.Conclusion  Treatment with sustained doses of hepcidin diminishes plasma iron concentrations in Hfe−/− mice.
Practical application and clinical impact of the WHO histopathological criteria on bone marrow biopsy for the diagnosis of essential thrombocythemia versus prefibrotic primary myelofibrosis
Authors: Brousseau Maud , Parot‐Schinkel Elsa , Moles Marie‐Pierre , Boyer Françoise , Hunault Mathilde , Rousselet Marie‐Christine 
Published: April 2010

Brousseau M, Parot‐Schinkel E, Moles M‐P, Boyer F, Hunault M & Rousselet M‐C (2010) Histopathology56, 758‐767 Practical application and clinical impact of the WHO histopathological criteria on bone marrow biopsy for the diagnosis of essential thrombocythemia versus prefibrotic primary myelofibrosisAims:  To evaluate the feasibility of the histopathological diagnosis of prefibrotic–early primary myelofibrosis (PM) as described in the World Health Organization (WHO) classification and to evaluate the clinical implications of prefibrotic–early PM in a series of patients previously diagnosed as having essential thrombocythemia (ET) according to the Polycythemia Vera Study Group criteria.Methods and results:  WHO criteria were applied to bone marrow biopsy specimens by two pathologists who then reclassified 127 cases as 102 ET (80.3%), 18 prefibrotic–early PM (14.2%) and seven fibrotic PM (5.5%). In 45 cases (35%), the final diagnosis was only reached by consensus. The megakaryocytic criteria that best discriminated between ET and prefibrotic–early PM were an increased nucleo–cytoplasmic ratio, presence of cloudlike nuclei, hyperchromatic‐dysplastic nuclei, paratrabecular megakaryocytes and tight clusters. A histological score discriminated between ET (score ≤3) and PM (score ≥6), but 21 cases showed an intermediate ambiguous score. No significant differences were observed at diagnosis and at follow‐up (median time 93 months) for thrombosis, major haemorrhage, laboratory data, transformation into overt myeloid metaplasia and survival.Conclusions:  The distinction between ET and prefibrotic–early PM is impaired by subjectivity in pathological practice and is of questionable clinical relevance, at least when considering individual patients.
Fibroblast growth factor (FGF)‐23 and fetuin‐A in calcified carotid atheroma
Authors: Voigt Mathias , Fischer Dagmar‐Christiane , Rimpau Max , Schareck Wolfgang , Haffner Dieter 
Published: April 2010

Voigt M, Fischer D‐C, Rimpau M, Schareck W & Haffner D (2010) Histopathology56, 775–788 Fibroblast growth factor (FGF)‐23 and fetuin‐A in calcified carotid atheromaAims:  Human atheroma calcification occurs secondary to repetitive injury/remodelling of the vessel wall and might be initiated by adherence of mineral‐loaded fetuin‐A whether or not professional matrix mineralizing cells are present. The aim was to investigate the contribution of fibroblast growth factor (FGF)‐23 to ectopic mineralization.Methods and results:  Serial sections of formalin‐fixed paraffin‐embedded human carotid atheroma (n = 54) were investigated with respect to (i) size and distribution of calcific deposits, (ii) indicators of chondrogenic/osteogenic transformation, and (iii) expression of fetuin‐A and FGF‐23. All specimens were calcified and SOX‐9, collagen type II, cathepsin‐K, fetuin‐A and FGF‐23 expression was seen in 46, 53, 53, 54 and 48 specimens, respectively. The intracellular detection of FGF‐23 (45/48) indicates local synthesis. Whereas fetuin‐A expression was seen also within areas of vascular smooth muscle actin‐positive cells adjacent to calcific deposits, FGF‐23 expression was apparently restricted to the mineralization‐prone areas. Both local expression and FGF‐23 serum concentrations were significantly associated with the degree of atheroma calcification.Conclusions:  Besides the induction of bone islets and subsequent mineral deposition, severe remodelling of the vessel wall is sufficient to create a mineralizable fetuin‐A‐attracting microenvironment. FGF‐23 might contribute to the formation of proper mineral, i.e. control local phosphate concentration.
Genomic and immunophenotypical differences between hepatocellular carcinoma with and without cirrhosis
Authors: Tretiakova Maria S , Shabani‐Rad Meer T , Guggisberg Kelly , Hart John , Anders Robert A , Gao Zu‐hua 
Published: April 2010

Tretiakova M S, Shabani‐Rad M T, Guggisberg K, Hart J, Anders R A & Gao Z‐h (2010) Histopathology 56, 683–693 Genomic and immunophenotypical differences between hepatocellular carcinoma with and without cirrhosisAims:  To compare the expression of genes involved in p53, Wnt/β‐catenin, and retinoblastoma (Rb) 1 pathways between cirrhosis‐associated hepatocellular carcinoma (HCC‐C) and hepatocellular carcinoma arising in non‐cirrhotic liver (HCC‐NC).Methods and results:  The gene expression profile was analysed using oligo‐DNA arrays, and then validated at protein level in a tissue microarray using immunohistochemistry. Compared with their background non‐neoplastic liver tissue, HCC‐C showed a significantly higher rate of p53, β‐catenin (protein only) and cyclin D1 expression, whereas HCC‐NC showed a significantly higher rate of p21Waf1/cip1 and p27Kip1 expression. HCC‐C had a significantly higher rate of p53 expression and a significantly lower rate of p21waf1/cip1 expression than HCC‐NC. There was no statistically significant association between the expression of genetic markers and tumour histological grade, underlying aetiology, or lymphovascular invasion. Aberrant β‐catenin expression was more commonly seen in single tumours in comparison with multiple tumours. Increased p16INK4 and p21waf1/cip1 expression was more commonly observed in large‐sized tumours (>50 mm) than small‐sized tumours.Conclusions:  Alteration of the p53 pathway plays a more important role in the pathogenesis of HCC‐C, whereas alterations in cell cycle regulators p21waf1/cip1 and p27Kip1 play a more important role in the pathogenesis of HCC‐NC.
Maximal heat dissipation capacity and hyperthermia risk: neglected key factors in the ecology of endotherms
Authors: Speakman John R. , Król Elżbieta 
Published: April 2010

Summary1. The role of energy in ecological processes has hitherto been considered primarily from the standpoint that energy supply is limited. That is, traditional resource‐based ecological and evolutionary theories and the recent ‘metabolic theory of ecology’ (MTE) all assume that energetic constraints operate on the supply side of the energy balance equation.2. For endothermic animals, we provide evidence suggesting that an upper boundary on total energy expenditure is imposed by the maximal capacity to dissipate body heat and therefore avoid the detrimental consequences of hyperthermia – the heat dissipation limit (HDL) theory. We contend that the HDL is a major constraint operating on the expenditure side of the energy balance equation, and that processes that generate heat compete and trade‐off within a total boundary defined by heat dissipation capacity, rather than competing for limited energy supply.3. The HDL theory predicts that daily energy expenditure should scale in relation to body mass (Mb) with an exponent of about 0·63. This contrasts the prediction of the MTE of an exponent of 0·75.4. We compiled empirical data on field metabolic rate (FMR) measured by the doubly‐labelled water method, and found that they scale toMbwith exponents of 0·647 in mammals and 0·658 in birds, not significantly different from the HDL prediction (P > 0·05) but lower than predicted by the MTE (P < 0·001). The same statistical result was obtained using phylogenetically independent contrasts analysis. Quantitative predictions of the model matched the empirical data for both mammals and birds. There was no indication of curvature in the relationship between LogeFMR and LogeMb.5. Together, these data provide strong support for the HDL theory and allow us to reject the MTE, at least when applied to endothermic animals.6. The HDL theory provides a novel conceptual framework that demands a reframing of our views of the interplay between energy and the environment in endothermic animals, and provides many new interpretations of ecological and evolutionary phenomena.
Functional changes induced by psychological stress are not enough to cause intestinal inflammation in Sprague–Dawley rats
Authors: Jorge E. , Fernández J. A. , Torres R. , Vergara P. , Martin M. T. 
Published: April 2010

AbstractBackground It is well known that stress contributes to the perpetuation of several gastrointestinal diseases. However, its role as a trigger of the inflammatory process in absence of other putative contributing factors remains controversial. Our aim was to elucidate whether stressper secan induce a primary gut inflammation in non‐predisposed rats.Methods Male Sprague–Dawley rats were divided in sham and stress groups. Chronic stress was induced by subjecting animals 1 h day−1to wrap restraint or water avoidance stress alternatively for five consecutive days, as a model of ongoing life stress.Key Results Chronic stress induced a significant decrease in body weight gain without changes in food intake and an increase in frequency of defecation. Electromiografic (EMG) study showed that the duration of the migrating motor cycles (MMCs), but not its frequency, was shortened in stressed animals compared with non‐stress conditions. Moreover, stressful stimulus caused mucosal mast cell hyperplasia and a decrease of iNOS mRNA expression. Bacterial translocation observed in stressed animals was not related to changes in epithelial barrier function and was not enough to induce intestinal inflammation.Conclusions & Inferences Decreased MMC duration, mast cell hyperplasia and decreased mRNA iNOS expression, but not altered epithelial barrier function, could be factors implicated in bacterial translocation‐induced by chronic stress. However, these changes are not sufficient to induce intestinal inflammation in stress non‐susceptible strain of rats.
Differentiation of metallicolous and non‐metallicolous Salix caprea populations based on phenotypic characteristics and nuclear microsatellite (SSR) markers
Authors: PUSCHENREITER MARKUS , TÜRKTAŞ MINE , SOMMER PETER , WIESHAMMER GERLINDE , LAAHA GREGOR , WENZEL WALTER W. , HAUSER MARIE‐THERES 
Published: April 2010

ABSTRACTThe Salicaceae family comprises a large number of high‐biomass species with remarkable genetic variability and adaptation to ecological niches. Salix caprea survives in heavy metal contaminated areas, translocates and accumulates Zn/Cd in leaves. To reveal potential selective effects of long‐term heavy metal contaminations on the genetic structure and Zn/Cd accumulation capacity, 170 S. caprea isolates of four metal‐contaminated and three non‐contaminated middle European sites were analysed with microsatellite markers using Wright's F statistics. The differentiation of populations North of the Alps are more pronounced compared to the Southern ones. By grouping the isolates based on their contamination status, a weak but significant differentiation was calculated between Northern metallicolous and non‐metallicolous populations. To quantify if the contamination and genetic status of the populations correlate with Zn/Cd tolerance and the accumulation capacity, the S. caprea isolates were exposed to elevated Cd/Zn concentrations in perlite‐based cultures. Consistent with the genetic data nested anova analyses for the physiological traits find a significant difference in the Cd accumulation capacity between the Northern and Southern populations. Our data suggest that natural populations are a profitable source to uncover genetic mechanisms of heavy metal accumulation and biomass production, traits that are essential for improving phytoextraction strategies.
Rosiglitazone attenuates hypoxia‐induced pulmonary arterial hypertension in rats
Authors: KIM Eun Kyung , LEE Ji‐Hyun , OH Yeon‐Mock , LEE Yun‐Song , LEE Sang‐Do 
Published: April 2010

ABSTRACTBackground and objective:  Expression of peroxisome proliferator‐activated receptor gamma (PPARγ) is decreased in the lungs of patients with pulmonary hypertension, and PPARγ ligands have been associated with the release of vasoactive substances from vascular endothelial cells and prevention of vascular remodelling. We hypothesized that PPARγ may play a critical role in the development of pulmonary hypertension induced by chronic hypoxia.Methods:  Male adult Sprague‐Dawley rats were exposed to normoxia, normoxia and rosiglitazone (8 mg/kg orally, 5 days/week), hypoxia (12% inspired O2 fraction), or hypoxia and rosiglitazone for 4 weeks. On the last day of the fourth week, pulmonary arterial pressure was measured and morphological changes in pulmonary vessels were assessed. The expression of PPARγ, endothelin (ET)‐1 and vascular endothelial growth factor (VEGF) was also analysed.Results:  Rosiglitazone inhibited the development of pulmonary hypertension, and pulmonary vascular remodelling induced by chronic hypoxia. PPARγ expression was decreased and expression of ET‐1 and VEGF was increased in lung tissues of the hypoxia group. Rosiglitazone treatment prevented the hypoxia‐induced reduction in PPARγ expression, and restored ET‐1 and VEGF expression almost to the levels of the normoxia group.Conclusions:  Rosiglitazone inhibited the development of pulmonary hypertension induced by chronic hypoxia, perhaps by reversing the changes in PPARγ, ET‐1 and VEGF expression induced by hypoxia. These findings indicate that rosiglitazone may be beneficial in the treatment of chronic hypoxic pulmonary hypertension.
Probable role of β2‐adrenergic receptor gene haplotype in high‐altitude pulmonary oedema
Authors: STOBDAN Tsering , KUMAR Ram , MOHAMMAD Ghulam , THINLAS Tashi , NORBOO Tsering , IQBAL Mohammad , PASHA M.A. Qadar 
Published: April 2010

ABSTRACTBackground and objective:  The role of β2‐adrenergic receptor (ADRB2) in pulmonary oxygenation has been ascertained during altitude acclimatization, physical performance and lung fluid clearance, but little is known about its association with high‐altitude pulmonary oedema (HAPE), a non‐cardiogenic pulmonary oedema.Methods:  In a case–control study, 110 unrelated HAPE patients (HAPE‐p) and 143 unrelated HAPE‐resistant (HAPE‐r) controls matched on age and ethnicity were used to examine the association between eight single nucleotide polymorphisms (SNP) and disease. The eight SNP including three tag‐SNP were genotyped from promoter and exonic regions of ADRB2. Robust methods for predicting geneotype–phenotype interactions, for example, multidimensional reduction (MDR) and moving‐window haplotype analysis were applied.Results:  The haplotypes from 46A/G and 79C/G SNP of ADRB2 were associated with HAPE. The MDR model depicting disease association through genotype–genotype and genotype–phenotype interaction included SNP 46A/G, 79C/G and 523C/A. Its haplotype 46G_79C_523C was significantly overrepresented in HAPE‐r (P = 0.0001; χ2 = 14.95; OR = 4.52; 95% CI: 1.98–10.3). The global haplotype test showed significant association with HAPE (LRχ2 = 86.69, P < 0.0001). A moving‐window analysis revealed that haplotype –367C/T_46A/G_79C/G differed significantly between HAPE‐p and HAPE‐r (LRχ2 = 22.5, P = 0.002). The MDR model depicted SNP 46A/G, 79C/G and 523C/A as the best combination predicting disease.Conclusions:  The haplotypes of ADRB2 consisting of the SNP, 46A/G and 79C/G, have a greater power for predicting HAPE.
The Strategic Nexus of Offshoring and Outsourcing Decisions
Authors: Mudambi Ram , Venzin Markus 
Published: April 2010

abstractOne important effect of the increasing integration of the world economy is the rising importance of possibilities to offshore and outsource value‐creating activities. In many industries, firms are able to disaggregate their value chains into smaller parts. This process allows for a less path‐dependent approach to the firm's ideal location profile (through offshoring and relocation) and control strategies (through outsourcing). This article argues that optimal decisions regarding individual processes recognize the linkages of these processes with the firm's entire value chain. The article explores the magnitude, sequence, and dynamics of interdependent decisions regarding the location and control of various parts of the value chain. By using case illustrations from the mobile handset and financial services industries, this article provides a novel perspective on the disintegration, mobility, and reintegration of value chain activities in a global context.
Does Urban Concentration/Dispersion Affect Immigrants' Professional Opportunities? The case of the Porto Metropolitan Area
Authors: REBELO EMÍLIA MALCATA 
Published: April 2010

AbstractThis article aims to test the hypothesis that urban concentration/dispersion characteristics exert an influence on the social and professional attainment levels reached by different immigrant groups in northern Portugal. I propose a theoretical and empirical methodology for analysing the impact that concentrated or dispersed neighbourhoods exert on immigrants' social and professional opportunities. The latter are assessed in terms of professional success, and a relationship is established between the professional levels reached by different immigrant groups and the territorial characteristics inherent to each group, as well as current concentration/dispersion patterns of land use. I also design an integrated information system to monitor the access of different population groups to professional opportunities, and to support municipal decisions in matters of immigrants' social, economic and cultural integration. Then I discuss how joint territorial planning policies, urbanization processes, ethnic features, the labour and housing markets and sociological assimilation networks have performed in Portugal's northern region in general, and the Porto metropolitan area in particular, both in launching local strategic economic development and in successfully integrating immigrants within the professional socio‐economic fabric.Résumé Cet article teste l'hypothèse selon laquelle les caractéristiques de la concentration‐dispersion urbaine exercent une influence sur les niveaux sociaux et professionnels atteints par différents groupes d'immigrants dans le nord du Portugal. Une méthodologie théorique et empirique est proposée pour analyser l'impact des quartiers, selon leur concentration ou dispersion, sur les opportunités sociales et professionnelles des immigrants. Ces dernières sont évaluées en termes de réussite professionnelle, et un lien est établi entre les niveaux professionnels atteints par différents groupes d'immigrants et les caractéristiques territoriales propres à chaque groupe, ainsi que les schémas d'occupation des sols en termes de concentration‐dispersion. De plus, un système d'information intégré est créé pour suivre l'accès des différents groupes de population aux opportunités professionnelles, et accompagner les décisions municipales en matière d'intégration sociale, économique et culturelle des immigrants. Est ensuite analysée la manière dont les politiques conjointes d'aménagement territorial, les processus d'urbanisation, les caractères ethniques, les marchés du travail et du logement, et les réseaux d'assimilation sociologique ont fonctionné dans la région nord du Portugal en général, et dans la zone métropolitaine de Porto en particulier, à la fois en insufflant un développement économique stratégique local et en réussissant à intégrer les immigrants dans le tissu socio‐économique professionnel.
Exposure to potentially traumatic events in early childhood: differential links to emergent psychopathology
Authors: Briggs‐Gowan Margaret J. , Carter Alice S. , Clark Roseanne , Augustyn Marilyn , McCarthy Kimberly J. , Ford Julian D. 
Published: April 2010

Objective:  To examine associations between exposure to potentially traumatic events (PTEs) and clinical patterns of symptoms and disorders in preschool children.Method:  Two hundred and thirteen referred and non‐referred children, ages 24 to 48 months (MN = 34.9, SD = 6.7 months) were studied. Lifetime exposure to PTEs (family violence and non‐interpersonal events) and recent stressful life events were assessed with the Preschool Age Psychiatric Assessment (PAPA) and Child Life Events Scale. Child psychiatric symptoms and disorders were assessed with parent‐reports in the PAPA, a comprehensive, developmentally sensitive interview. Sociodemographic risk, parental anxiety and depressive symptoms (Center for Epidemiologic Studies Depression, Beck Anxiety Inventory), and child developmental level (Mullen Scales of Early Learning) also were assessed.Results:  Violence exposure was broadly associated with psychiatric status in the areas of depression, separation anxiety, posttraumatic stress, and conduct problems, whereas potentially traumatic non‐interpersonal exposure was associated with phobic anxiety. The majority of the associations between violence exposure and preschoolers’ symptoms were significant even when other key factors, including economic disadvantage and parental mood and anxiety symptoms, were controlled statistically. However, parental depressive/anxious symptoms may have partially or fully mediated the relationships between violence exposure and depressive and conduct symptoms.Conclusions:  Evidence of robust associations between violence exposure and early childhood internalizing and externalizing disorders and symptoms highlights the need for longitudinal prospective research concerning neurodevelopmental mechanisms and pathways. Findings underscore the relevance of assessing trauma exposure, particularly interpersonal violence, to identify young children at risk.