bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANALYSING THE RURAL VITALITY ARGUMENT FOR RESIDENTIAL DEVELOPMENT: LINKING DISCOURSES AND ACTUAL SPATIAL DEVELOPMENTS
Authors: VAN RIJ EVELIEN , KOOMEN ERIC 
Published: November 2010

ABSTRACTIn the heated debate on new residential development in the countryside, rural vitality is used in three different discourses: the agri‐rural, utilitarian and hedonist. Discussions on the future of the Dutch countryside in general and a designated National Landscape north of Amsterdam in particular illustrate how the term rural vitality, depending on the discourse, is used to either support or oppose residential development. As in the region studied, the utilitarian discourse is increasingly important and its consequences – residential development in a highly valued landscape – are most controversial, we chose to evaluate its validity. This quantitative evaluation makes use of a geographical information system (GIS) and highly detailed spatial data. The results show no clear relationship between the construction of houses and different indicators of rural vitality such as employment and facility levels. Therefore, we question the validity of the utilitarian discourses' argument for supporting residential development.
Training evaluation in Italian corporate universities: a stakeholder‐based analysis
Authors: Guerci Marco , Bartezzaghi Emilio , Solari Luca 
Published: November 2010

Corporate universities have emerged as a mechanism for providing companies with a wide variety of training and development activities. They are a recent but under‐researched phenomenon, and given their substantial budgets, it might be expected that they would wish to evaluate what they do. The authors explore the evaluation practices of six Italian corporate universities, paying particular attention to the means by which these practices are tailored to the needs of the various stakeholders. Stakeholder‐based evaluation provides the theoretical framework for the study.The literature suggests that much evaluation of training focuses on a single stakeholder, the shareholder, and that practice draws heavily on Kirkpatrick's hierarchical model. In the context of the corporate university, however, the authors find that multi‐stakeholder evaluation is used in practice. Moreover, various aspects of corporate university performance were evaluated, and data were supplied to stakeholders depending on the nature of their involvement. Stakeholder‐based evaluation is argued to be a useful framework where there are a number of stakeholders, but training evaluation models other than the hierarchical one are needed if all relevant training factors are to be evaluated. The implications for research and practice are discussed.
Biomechanical properties and innervation of the female caveolin‐1‐deficient detrusor
Authors: Sadegh Mardjaneh Karbalaei , Ekman Mari , Rippe Catarina , Sundler Frank , Wierup Nils , Mori Michiko , Uvelius Bengt , Swärd Karl 
Published: November 2010

BACKGROUND AND PURPOSE Caveolin‐1‐deficiency is associated with substantial urogenital alterations. Here, a mechanical, histological and biochemical characterization of female detrusors from wild‐type and caveolin‐1‐deficient (KO) mice was made to increase the understanding of detrusor changes caused by lack of caveolae.EXPERIMENTAL APPROACH Length–tension relationships were generated, and we recorded responses to electrical field stimulation, the muscarinic receptor agonist carbachol and the purinoceptor agonist ATP. Tyrosine nitration and the contents of caveolin‐1, cavin‐1, muscarinic M3 receptors, phospholipase Cβ1, muscle‐specific kinase (MuSK) and L‐type Ca2+ channels were determined by immunoblotting. Innervation was assessed by immunohistochemistry.KEY RESULTS Bladder to body weight ratio was not changed, nor was there any change in the optimum circumference for force development. Depolarization‐ and ATP‐induced stress was reduced, as was carbachol‐induced stress between 0.1 and 3 µM, but the supramaximal relative (% K+) response to carbachol was increased, as was M3 expression. The scopolamine‐sensitive component of the electrical field stimulation response was impaired, and yet bladder nerves contained little caveolin‐1. The density of cholinergic nerves was unchanged, whereas CART‐ and CGRP‐positive nerves were reduced. Immunoblotting revealed loss of MuSK.CONCLUSIONS AND IMPLICATIONS Ablation of caveolae in the female detrusor leads to generalized impairment of contractility, ruling out prostate hypertrophy as a contributing factor. Cholinergic neuroeffector transmission is impaired without conspicuous changes in the density of cholinergic nerves or morphology of their terminals, but correlating with reduced expression of MuSK.
Mechanisms for anti‐inflammatory effects of 1‐[15(S)‐hydroxyeicosapentaenoyl] lysophosphatidylcholine, administered intraperitoneally, in zymosan A‐induced peritonitis
Authors: Hung Nguyen Dang , Kim Mee Ree , Sok Dai‐Eun 
Published: November 2010

BACKGROUND AND PURPOSELysophosphatidylcholines (lysoPCs) with polyunsaturated acyl chains are known to exert anti‐inflammatory actions. 15‐Lipoxygeanation is crucial for anti‐inflammatory action of polyunsaturated acylated lysoPCs. Here, the anti‐inflammatory actions of 1‐(15‐hydroxyeicosapentaenoyl)‐lysoPC (15‐HEPE‐lysoPC) and its derivatives were examined in a mechanistic analysis.EXPERIMENTAL APPROACHAnti‐inflammatory actions of 15‐HEPE‐lysoPC in zymosan A‐induced peritonitis of mice were examined by measuring plasma leakage and leucocyte infiltration, and determining levels of lipid mediators or cytokines.KEY RESULTSWhen each lysoPC, administered i.v., was assessed for its ability to suppress zymosan A‐induced plasma leakage, 15‐HEPE‐lysoPC was found to be more potent than 1‐(15‐hydroperoxyeicosapentaenoyl)‐lysoPC or 1‐eicosapentaenoyl‐lysoPC. Separately, i.p. administration of 15‐HEPE‐lysoPC markedly inhibited plasma leakage, in contrast to 15‐HEPE, which had only a small effect. 15‐HEPE‐lysoPC also decreased leucocyte infiltration. Moreover, it reduced the formation of LTC4and LTB4, 5‐lipoxygenation products, as well as the levels of pro‐inflammatory cytokines. The time‐course study indicated that 15‐HEPE‐lysoPC might participate in both the early inflammatory phase and resolution phase. Additionally, 15‐HEPE‐lysoPC administration caused a partial suppression of LTC4‐induced plasma leakage and LTB4‐induced leucocyte infiltration. In the metabolism study, peritoneal exudate was shown to contain lysoPC‐hydrolysing activity, crucial for anti‐inflammatory activity, and a system capable of generating lipoxin A from 15‐hydroxy eicosanoid precursor.CONCLUSIONS AND IMPLICATIONS15‐HEPE‐lysoPC, a precursor for 15‐HEPE in target cells, induced anti‐inflammatory actions by inhibiting the formation of pro‐inflammatory leukotrienes and cytokines, and by enhancing the formation of lipoxin A. 15‐HEPE‐lysoPC might be one of many potent anti‐inflammatory lipidsin vivo.
Hydrogen sulphide protects mouse pancreatic β‐cells from cell death induced by oxidative stress, but not by endoplasmic reticulum stress
Authors: Taniguchi S , Kang L , Kimura T , Niki I 
Published: November 2010

BACKGROUND AND PURPOSE Hydrogen sulphide (H2S), a potentially toxic gas, is also involved in the neuroprotection, neuromodulation, cardioprotection, vasodilatation and the regulation of inflammatory response and insulin secretion. We have recently reported that H2S suppresses pancreatic β‐cell apoptosis induced by long‐term exposure to high glucose. Here we examined the protective effects of sodium hydrosulphide (NaHS), an H2S donor, on various types of β‐cell damage.EXPERIMENTAL APPROACH Isolated islets from mice or the mouse insulinoma MIN6 cells were cultured with palmitate, cytokines (a mixture of tumour necrosis factor‐α, interferon‐γ and interleukin‐1β), hydrogen peroxide, thapsigargin or tunicamycin with or without NaHS. We examined DNA fragmentation, caspase‐3 and ‐7 activities and reactive oxygen species (ROS) production in the treated cells thereafter. Apoptotic cell death in isolated islets was also assessed by the terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labelling (TUNEL) method.KEY RESULTS NaHS suppressed DNA fragmentation and the activities of caspase‐3 and ‐7 induced by palmitate, the cytokines or hydrogen peroxide. In contrast, NaHS failed to protect islets and MIN6 cells from apoptosis induced by thapsigargin and tunicamycin, both of which cause endoplasmic reticulum stress. NaHS suppressed ROS production induced by cytokines or hydrogen peroxide but it had no effect on ROS production in thapsigargin‐treated cells. NaHS increased Akt phosphorylation in MIN6 cells treated with cytokines but not in cells treated with thapsigargin. Treatment with NaHS decreased TUNEL‐positive cells in cytokine‐exposed islets.CONCLUSIONS AND IMPLICATIONS H2S may prevent pancreatic β‐cells from cell apoptosis via an anti‐oxidative mechanism and the activation of Akt signalling.
Rescuing iron‐overloaded macrophages by conservative relocation of the accumulated metal
Authors: Sohn Yang‐Sung , Mitterstiller Anna‐Maria , Breuer William , Weiss Guenter , Cabantchik Z Ioav 
Published: November 2010

BACKGROUND AND PURPOSE Systemic iron deficiency concomitant with macrophage iron retention is characteristic of iron‐refractory anaemias associated with chronic disease. The systemic misdistribution of iron, which is further exacerbated by parenteral iron supplementation, is mainly attributable to iron retention exerted on resident macrophages by hepcidin‐mediated down‐regulation of the iron exporter ferroportin. We aimed at developing an experimental macrophage‐based cell model that recapitulates pathophysiological features of iron misdistribution found in chronic disorders and use it as a screening platform for identifying agents with the potential for relocating the accumulated metal and restoring affected functions.EXPERIMENTAL APPROACH A RAW macrophage subline was selected as cell model of iron retention based on their capacity to take up polymeric iron or aged erythrocytes excessively, resulting in a demonstrable increase of cell labile iron pools and oxidative damage that are aggravated by hepcidin.KEY RESULTS This model provided a three‐stage high throughput screening platform for identifying agents with the combined ability to: (i) scavenge cell iron and thereby rescue macrophage cells damaged by iron‐overload; (ii) bypass the ferroportin blockade by conveying the scavenged iron to other iron‐starved cells in co‐culture via transferrin but (iii) without promoting utilization of the scavenged iron by intracellular pathogens. As test agents we used chelators in clinical practice and found the oral chelator deferiprone fulfilled essentially all of the three criteria.CONCLUSIONS AND IMPLICATIONS We provide a proof of principle for conservative iron relocation as complementary therapeutic approach for correcting the misdistribution of iron associated with chronic disease and exacerbated by parenteral iron supplementation.
Functional antagonism of β‐adrenoceptor subtypes in the catecholamine‐induced automatism in rat myocardium
Authors: Boer DC , Bassani JWM , Bassani RA 
Published: November 2010

BACKGROUND AND PURPOSEMyocardial automatism and arrhythmias may ensue during strong sympathetic stimulation. We sought to investigate the relevant types of adrenoceptor, as well as the role of phosphodiesterase (PDE) activity, in the production of catecholaminergic automatism in atrial and ventricular rat myocardium.EXPERIMENTAL APPROACHThe effects of adrenoceptor agonists on the rate of spontaneous contractions (automatic response) and the amplitude of electrically evoked contractions (inotropic response) were determined in left atria and ventricular myocytes isolated from Wistar rats.KEY RESULTSCatecholaminergic automatism was Ca2+‐dependent, as it required a functional sarcoplasmic reticulum to be exhibited. Although both α‐ and β‐adrenoceptor activation caused inotropic stimulation, only β1‐adrenoceptors seemed to mediate the induction of spontaneous activity. Catecholaminergic automatism was enhanced and suppressed by β2‐adrenoceptor blockade and stimulation respectively. Inhibition of either PDE3 or PDE4 (by milrinone and rolipram, respectively) potentiated the automatic response of myocytes to catecholamines. However, only rolipram abolished the attenuation of automatism produced by β2‐adrenoceptor stimulation.CONCLUSIONS AND IMPLICATIONSα‐ and β2‐adrenoceptors do not seem to be involved in the mediation of catecholaminergic stimulation of spontaneous activity in atrial and ventricular myocardium. However, a functional antagonism of β1‐ and β2‐adrenoceptor activation was identified, the former mediating catecholaminergic myocardial automatism and the latter attenuating this effect. Results suggest that hydrolysis of cAMP by PDE4 is involved in the protective effect mediated by β2‐adrenoceptor stimulation.
Melatonin inhibits tachykinin NK2receptor‐triggered 5‐HT release from guinea pig isolated colonic mucosa
Authors: Kojima Shu‐ichi , Tohei Atsushi , Ikeda Masashi 
Published: November 2010

BACKGROUND AND PURPOSEMelatonin is involved in the regulation of colonic motility, and sensation, but little is known about the influence of melatonin on 5‐hydroxytryptamine (5‐HT) release from colonic mucosa. A tachykinin NK2receptor‐selective agonist, [β‐Ala8]‐neurokinin A4‐10[βAla‐NKA‐(4‐10)] can induce 5‐HT release from guinea pig colonic mucosa via NK2receptors on the mucosal layer. The present study was designed to determine the influence of melatonin on 5‐HT release from guinea pig colonic mucosa, evoked by the NK2receptor agonist, βAla‐NKA‐(4‐10).EXPERIMENTAL APPROACHThe effect of melatonin was investigated on the outflow of 5‐HT and its metabolite 5‐hydroxyindoleacetic acid (5‐HIAA) from muscle layer‐free mucosal preparations of guinea pig colon, using high‐performance liquid chromatography with electrochemical detection.KEY RESULTSMelatonin caused a sustained decline in the βAla‐NKA‐(4‐10)‐evoked 5‐HT outflow from the muscle layer‐free mucosal preparations, but failed to affect its metabolite 5‐HIAA outflow. The specific MT3receptor agonist, 5‐methoxycarbonylamino‐N‐acetyltryptamine mimicked the inhibitory effect of melatonin on βAla‐NKA‐(4‐10)‐evoked 5‐HT outflow. A MT3receptor antagonist prazosin shifted the concentration‐response curve of melatonin to the right in a concentration‐dependent manner and depressed the maximum effect, but neither a combined MT1/MT2receptor antagonist luzindole, nor a MT2receptor antagonist N‐pentanoyl‐2‐benzyltryptamine modified the concentration–response curve to melatonin.CONCLUSIONS AND IMPLICATIONSMelatonin inhibits NK2receptor‐triggered 5‐HT release from guinea pig colonic mucosa by acting at a MT3melatonin receptor located directly on the mucosal layer, without affecting 5‐HT degradation processes. Possible contributions of MT1/MT2melatonin receptors to the inhibitory effect of melatonin appear to be negligible. Melatonin may act as a modulator of excess 5‐HT release from colonic mucosa.
The glucocorticoid‐induced TNF receptor family‐related protein (GITR) is critical to the development of acute pancreatitis in mice
Authors: Galuppo M , Nocentini G , Mazzon E , Ronchetti S , Esposito E , Riccardi L , Sportoletti P , Di Paola R , Bruscoli S , Riccardi C , Cuzzocrea S 
Published: November 2010

BACKGROUND AND PURPOSE Pancreatitis represents a life‐threatening inflammatory condition where leucocytes, cytokines and vascular endothelium contribute to the development of the inflammatory disease. The glucocorticoid‐induced tumour necrosis factor (TNF) receptor family‐related protein (GITR) is a costimulatory molecule for T lymphocytes, modulates innate and adaptive immune system and has been found to participate in a variety of immune responses and inflammatory processes. Our purpose was to verify whether inhibition of GITR triggering results in a better outcome in experimental pancreatitis.EXPERIMENTAL APPROACH In male GITR knock‐out (GITR−/−) and GITR+/+ mice on Sv129 background, acute pancreatitis was induced after i.p. administration of cerulein. Other experimental groups of GITR+/+ mice were also treated with different doses of Fc‐GITR fusion protein (up to 6.25 µg·mouse−1), given by implanted mini‐osmotic pump. Clinical score and pro‐inflammatory parameters were evaluated.KEY RESULTS A less acute pancreatitis was found in GITR−/− mice than in GITR+/+ mice, with marked differences in oedema, neutrophil infiltration, pancreatic dysfunction and injury. Co‐treatment of GITR+/+ mice with cerulein and Fc‐GITR fusion protein (6.25 µg·mouse−1) decreased the inflammatory response and tissue injury, compared with treatment with cerulein alone. Inhibition of GITR triggering was found to modulate activation of nuclear factor κB as well as the production of TNF‐α, interleukin‐1β, inducible nitric oxide synthase, nitrotyrosine, poly‐ADP‐ribose, intercellular adhesion molecule‐1 and P‐selectin.CONCLUSIONS AND IMPLICATIONS The GITR‐GITR ligand system is crucial to the development of acute pancreatitis in mice. Our results also suggest that the Fc‐GITR fusion protein could be useful in the treatment of acute pancreatitis.
Microarray analysis of nemorosone‐induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR)
Authors: Holtrup Frank , Bauer Andrea , Fellenberg Kurt , Hilger Ralf A , Wink Michael , Hoheisel Jörg D 
Published: November 2010

BACKGROUND AND PURPOSE Pancreatic cancer is one of the leading cancer‐related causes of death due to high chemo‐resistance and fast metastasation. Nemorosone, a polycyclic polyprenylated acylphloroglucinol, has recently been identified as a promising anticancer agent. Here, we examine its growth‐inhibitory effects on pancreatic cancer cells. Based on transcription profiling, a molecular mode of action is proposed.EXPERIMENTAL APPROACH Nemorosone cytotoxicity was assessed by the resazurin proliferation assay on pancreatic cancer cells and fibroblasts. Apoptosis was determined by Annexin V/propidium iodide staining as well as cytochrome c and caspase activation assays. Staining with the voltage‐dependent dye JC‐1 and fluorescence microscopy were used to detect effects on mitochondrial membrane potential. Total RNA was isolated from treated cell lines and subjected to microarray analysis, subsequent pathway identification and modelling. Gene expression data were validated by quantitative polymerase chain reaction and siRNA‐mediated gene knock‐down.KEY RESULTS Nemorosone significantly inhibited cancer cell growth, induced cytochrome c release and subsequent caspase‐dependent apoptosis, rapidly abolished mitochondrial membrane potential and elevated cytosolic calcium levels, while fibroblasts were largely unaffected. Expression profiling revealed 336 genes to be affected by nemorosone. A total of 75 genes were altered in all three cell lines, many of which were within the unfolded protein response (UPR) network. DNA damage inducible transcript 3 was identified as a key regulator in UPR‐mediated cell death.CONCLUSIONS AND IMPLICATIONS Nemorosone could be a lead compound for the development of novel anticancer drugs amplifying the already elevated UPR level in solid tumours, thus driving them into apoptosis. This study forms the basis for further investigations identifying nemorosone's direct molecular target(s).
Metformin inhibits HMGB1 release in LPS‐treated RAW 264.7 cells and increases survival rate of endotoxaemic mice
Authors: Tsoyi Konstantin , Jang Hwa Jin , Nizamutdinova Irina Tsoy , Kim Young Min , Lee Young Soo , Kim Hye Jung , Seo Han Geuk , Lee Jae Heun , Chang Ki Churl 
Published: November 2010

BACKGROUND AND PURPOSERecently, metformin, a well‐known anti‐diabetic drug, has been shown to possess anti‐inflammatory activities. This study investigated the effect of metformin on the expression of pro‐inflammatory cytokines including high mobility group box 1 (HMGB1) in lipopolysaccharide (LPS)‐treated animals and cells.EXPERIMENTAL APPROACHWe investigated whether metformin inhibits the release of HMGB1 in LPS‐treated RAW 264.7 cells and increases survival rate in endotoxaemic mice (lethal endotoxaemia was induced by an i.p. injection of LPS). This was achieved by a range of techniques including Western blotting, enzyme‐linked immunosorbent assay, specific pharmacological inhibitors, knock out of α1‐subunit of AMP‐activated protein kinase (AMPK) and recombinant HMGB1.KEY RESULTSBoth pre‐ and post‐treatment with metformin significantly improved survival of animals during lethal endotoxaemia (survival rate was monitored up to 2 weeks), decreased serum levels of tumour necrosis factor‐alpha (TNF‐α), interleukin‐1β, HMGB1 expression and myeloperoxidase activity in lungs. However, metformin failed to improve survival in endotoxaemic animals that had additionally been treated with recombinant HMGB1. In anin vitrostudy, metformin dose‐dependently inhibited production of pro‐inflammatory cytokines and HMGB1 release. Metformin activated AMPK by its phosphorylation. Compound C (pharmacological inhibitor of AMPK) and siAMPKα1 reversed the anti‐inflammatory effect of metformin in LPS‐treated cells.CONCLUSIONS AND IMPLICATIONSOur data indicate that metformin significantly attenuates the pro‐inflammatory response induced by LPS bothin vivoandin vitro. Metformin improved survival in a mouse model of lethal endotoxaemia by inhibiting HMGB1 release. AMPK activation was implicated as one of the mechanisms contributing to this inhibition of HMGB1 secretion.
Improving planning, design, reporting and scientific quality of animal experiments by using the Gold Standard Publication Checklist, in addition to the ARRIVE guidelines
Authors: Hooijmans Carlijn R , de Vries Rob , Leenaars Marlies , Curfs Jo , Ritskes‐Hoitinga Merel 
Published: November 2010

Several studies have demonstrated serious omissions in the way research that use animals is reported. In order to improve the quality of reporting of animal experiments, the Animals in research: reporting in vivo experiments (ARRIVE) Guidelines were published in the British Journal of Pharmacology in August 2010.However, not only the quality of reporting of completed animal studies needs to be improved, but also the design and execution of new experiments. With both these goals in mind, we published the Gold Standard Publication Checklist (GSPC) in May 2010, a few months before the ARRIVE guidelines appeared. In this letter, we compare the GSPC checklist with the ARRIVE Guidelines. The GSPC describes certain items in more detail, which makes it both easier to use when designing and conducting an experiment and particularly suitable for making systematic reviews of animal studies more feasible. In order to improve not only the reporting but also the planning, design, execution and thereby, the scientific quality of animal experiments, we strongly recommend to all scientists involved in animal experimentation and to editors of journals publishing animal studies to take a closer look at the contents of both the ARRIVE guidelines and GSPC, and select the set of guidelines which is most appropriate for their particular situation.LINKED ARTICLES To view the article by Kilkenny et al. visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00872.x. To view the editorial by McGrath et al. visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00873.x