bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of brain‐to‐blood efflux transport activity of low‐density lipoprotein receptor‐related protein‐1 (LRP‐1) for amyloid‐β peptide(1–40) in mouse: involvement of an LRP‐1‐independent pathway
Authors: Ito Shingo , Ueno Takashi , Ohtsuki Sumio , Terasaki Tetsuya 
Published: March 2010

J. Neurochem.(2010)113, 1356–1363.AbstractThe contribution of low‐density lipoprotein receptor‐related protein‐1 (LRP‐1) to the brain‐to‐blood amyloid‐β peptide (Aβ) efflux transport across the blood‐brain barrier (BBB) remains controversial. The purpose of the present study was to clarify whether or not LRP‐1 plays a role in efflux transport of Aβ at the BBB. After microinjection of [125I]activated α2‐macroglobulin (α2M), a typical LRP‐1 ligand, into mouse secondary somatosensory cortex region under ketamine‐xylazine anesthesia, residual radioactivity was not significantly decreased up to 90 min, whereas after microinjection of [125I]human Aβ(1–40) [hAβ(1–40)], the residual radioactivity decreased time‐dependently. Co‐administration of receptor‐associated protein, an inhibitor of LRP‐1, did not influence [125I]hAβ(1–40) elimination from mouse brain, suggesting that members of the LDL receptor gene family, including LRP‐1, do not contribute to hAβ(1–40) elimination from mouse brain across the BBB. There was no significant difference between the uptakes of [125I]activated α2M and [14C]inulin by mouse brain slices, suggesting that activated α2M was not significantly bound to and/or taken up by parenchymal cells. In conclusion, our results show that LRP‐1 does not play a significant role in the brain‐to‐blood efflux transport of Aβ(1–40) at the mouse BBB, but an unidentified transporter(s) appears to be involved.
Glutamate receptor‐mediated phosphorylation of ezrin/radixin/moesin proteins is implicated in filopodial protrusion of primary cultured hippocampal neuronal cells
Authors: Kim Han‐Seop , Bae Chang‐Dae , Park Joobae 
Published: March 2010

J. Neurochem. (2010) 113, 1565–1576.AbstractPreviously, we reported the phosphorylation of moesin induced by electroconvulsive shock in rat brain and by glutamate in immortalized rat hippocampal cells. However, the function of phosphorylated moesin in differentiated neurons is not well understood. In this study, we observed that glutamate induces phosphorylation of ezrin/radixin/moesin proteins (ERM) in cultured hippocampal cells and that phosphorylated ERM localizes at the newly formed filopodia of neurites. The glutamate‐induced phosphorylation of ERM is calcium‐dependent, and inhibition of protein kinase C abolishes ERM phosphorylation as well as RhoA activation. The inhibitions of RhoA and RhoA kinase also diminishes the glutamate‐induced ERM phosphorylation in cultured hippocampal cells. The knock‐down of moesin or the inhibition of ERM phosphorylation results in the reduction of glutamate‐induced filopodia protrusion and diminishes the increase in active synaptic boutons induced by glutamate treatment. These results indicate that glutamate‐induced phosphorylation of ERM proteins in primary cultured differentiated hippocampal neurons is mediated by calcium‐dependent protein kinase C, RhoA and RhoA kinase, and the phosphorylated ERM protein is necessary for the formation of filopodial protrusion and may be involved in pre‐synaptic trafficking.
Adenosine A2A receptors in both bone marrow cells and non‐bone marrow cells contribute to traumatic brain injury
Authors: Dai Shuang‐Shuang , Li Wei , An Jian‐Hong , Wang Hao , Yang Nan , Chen Xing‐Yun , Zhao Yan , Li Ping , Liu Ping , Chen Jiang‐Fan , Zhou Yuan‐Guo 
Published: March 2010

J. Neurochem.(2010)113, 1536–1544.AbstractAdenosine A2A receptors (A2ARs) in bone marrow‐derived cells (BMDCs) are involved in regulation of inflammation and outcome in several CNS injuries; however their relative contribution to traumatic brain injury (TBI) is unknown. In this study, we created a mouse cortical impact model, and BMDC A2ARs were selectively inactivated in wild‐type (WT) mice or reconstituted in global A2AR knockout (KO) mice (i.e. inactivation of non‐BMDC A2ARs) by bone marrow transplantation. When compared with WT mice, selective inactivation of BMDC A2ARs significantly attenuated the neurological deficits, brain water content and cell apoptosis at 24 h post‐TBI as global A2AR KO did. However, compared with the A2AR KO mice, selective reconstitution of BMDC A2ARs failed to reinstate brain injury, indicating the contribution of the non‐BMDC A2AR to TBI. Furthermore, the protective outcome by selective inactivation of BMDC A2AR or broad inactivation of non‐BMDC A2ARs was accompanied with reduced CSF glutamate level and suppression of the inflammatory cytokines interleukin‐1, or interleukin‐1 and tumor necrosis factor‐α. These findings demonstrate that inactivation of A2ARs in either BMDCs or non‐BMDCs is sufficient to confer the protective effect as global A2AR KO against TBI, indicating the A2AR involvement in TBI by multiple cellular mechanisms of A2AR involvement including inhibition of glutamate release and inflammatory cytokine expressions.
A2badenosine receptors can change their spots
Authors: Cohen Michael V , Yang Xiulan , Downey James M 
Published: March 2010

Recently, a central role for the A2badenosine receptor in a variety of cardiovascular functions including inflammation, erectile function, coronary artery dilation, asthma and cardioprotection has been demonstrated. Despite this evidence, the low‐affinity A2badenosine receptor is still poorly understood. This receptor appears to be very promiscuous in its coupling. In most tissues, it couples to Gsmuch like its cousin, the A2aadenosine receptor, but in mast cells and now, most recently, in cardiac fibroblasts, the A2breceptor also couples to Gq. Because of its low affinity, this receptor was originally thought unlikely to play any important physiological role. But the sensitivity of A2badenosine receptors can be greatly increased by interaction with protein kinase C (PKC) making this receptor, under various conditions, both an activator and a target of PKC. We have recently documented a third coupling involving Gi. This plasticity and versatility of A2badenosine receptors position them as potential triggers of signalling in multiple signalling cascades in many physiological responses, making this a most interesting receptor indeed.This article is a commentary on Fenget al., pp. 1598–1607 of this issue. To view this paper visithttp://dx.doi.org/10.1111/j.1476‐5381.2009.00558.x
Pharmacological pre‐ and post‐conditioning with the sphingosine‐1‐phosphate receptor modulator FTY720 after myocardial ischaemia–reperfusion
Authors: Hofmann U , Hu K , Walter F , Burkard N , Ertl G , Bauersachs J , Ritter O , Frantz S , Bonz A 
Published: March 2010

Background and purpose:  Our recent experiments demonstrated that the Sphingosine‐1‐phosphate (S1P) receptor agonist FTY720 (2‐amino‐2‐[2‐(4‐octylphenyl)ethyl]‐1,3‐propanediol hydrochloride) improves recovery of function after myocardial ischaemia–reperfusion ex vivo. Therefore, we tested the hypothesis that pharmacological post‐conditioning with FTY720 reduces infarct size after myocardial ischaemia–reperfusion in vivo.Experimental approach:  Myocardial ischaemia was induced in Wistar rats by ligation of the left coronary artery for 45 min. FTY720 (0.5 mg·kg−1) was applied i.p. either once, before reperfusion, or twice, 24 h before myocardial ischaemia and before reperfusion. After 24 h reperfusion, we determined infarct size by triphenyltetrazolium chloride staining and granulocyte infiltration by immunohistochemistry. Tumour necrosis factor‐α (TNF)‐α concentration was determined by elisa. S1P receptor expression was studied by Western blot. Calcium transients were evaluated in Indo‐1‐loaded cardiomyocytes.Key results:  In both groups, FTY720 significantly reduced lymphocyte count in peripheral blood. FTY720 treatment attenuated granulocyte infiltration and TNF‐α protein expression in reperfused myocardium. However, both treatment regimens were not able to reduce infarct size. FTY720 increased mortality due to induction of fatal ventricular tachyarrhythmias when administered once before reperfusion, but protected against reperfusion arrhythmias when given 24 h prior to ischaemia. Pretreatment selectively down‐regulated S1P1 receptor expression within the myocardium. S1P receptor agonists did not induce calcium deregulation in cardiomyocytes.Conclusions and implications:  FTY720 applied during reperfusion did not reduce infarct size but increased mortality during myocardial ischaemia–reperfusion due to induction of arrhythmias. Pretreatment with FTY720 before ischaemia abrogated the deleterious pro‐arrhythmic effects without reducing infarct size.
Neuroprotective potential of CB1receptor agonists in anin vitromodel of Huntington's disease
Authors: Scotter EL , Goodfellow CE , Graham ES , Dragunow M , Glass M 
Published: March 2010

Background and purpose: The therapeutic potential of cannabinoids in Huntington's disease (HD) has been investigated by several groups with complex and sometimes contrasting results. We sought to examine key points of intersection between cannabinoid receptor 1 (CB1) signalling, survival and the formation of mutant huntingtin aggregates in HD.Experimental approach: Using a simplified pheochromocytoma (PC12) cell model of HD expressing exon 1 of wild‐type or mutant huntingtin, we assayed cell death and aggregate formation using high‐throughput cytotoxicity and image‐based assays respectively.Key results: CB1activation by HU210 conferred a small but significant level of protection against mutant huntingtin‐induced cell death.Pertussistoxin uncoupled HU210 from the inhibition of cAMP, preventing rescue of cell death. Phosphorylation of extracellular signal‐regulated kinase (ERK) was also critical to CB1‐mediated rescue. Conversely, treatments that elevated cAMP exacerbated mutant huntingtin‐induced cell death. Despite opposing effects on HD cell survival, both HU210 and compounds that elevated cAMP increased the formation of mutant huntingtin aggregates. The increase in aggregation by HU210 was insensitive toPertussistoxin and UO126, suggesting a G‐protein alpha subtype s (Gs)‐linked mechanism.Conclusions and implications: We suggest that the CB1receptor, through G‐protein alpha subtype i/o (Gi/o)‐linked, ERK‐dependent signal transduction, is a therapeutic target in HD. However the protective potential of CB1may be limited by promiscuous coupling to Gs, the stimulation of cAMP formation and increased aggregate formation. This may underpin the poor therapeutic efficacy of cannabinoids in more complex model systems and suggest that therapies that are selective for the Gi/o, ERK pathway may be of most benefit in HD.This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visithttp://dx.doi.org/10.1111/j.1476‐5381.2010.00831.x
Distribution of orthodontic services in Norway
Authors: Grytten Jostein , Skau Irene , Stenvik Arild 
Published: March 2010

Grytten J, Skau I, Stenvik A. Distribution of orthodontic services in Norway. Community Dent Oral Epidemiol 2010; 38: 267–273. © 2010 John Wiley & Sons A/SAbstract –  Background and objectives:  There is a lack of studies that have evaluated how different ways of organizing and financing orthodontic services perform with respect to access to care, and the cost of care. In Norway, orthodontic services for children and adolescents are partly financed by the state, and the size of the state subsidy depends on the severity of the malocclusion. Orthodontists have the freedom to establish a practice where they wish. The aim of this study was to examine whether there are inequalities with respect to access to orthodontic services in Norway, and to study the development of costs of the services from 2004 to 2007.Methods:  Data on mean waiting time for starting treatment and working hours in practice were collected using a questionnaire that was sent to all the orthodontists in the country (n = 165). The response rate was 74%. The number of patients who received treatment according to different criteria of need was recorded from data in each practice. Information about the development of costs for orthodontic treatment was obtained from the National Insurance Administration.Results:  In almost all the areas, waiting time for starting treatment was within clinically acceptable limits, and there were only small differences in supply of orthodontic treatment in different areas. Patients with the greatest need were given priority over patients with the least need, which is in line with the aims of the authorities. In 2007 the reimbursements for orthodontic treatment from the National Insurance Administration amounted to Euro 48 million. In deflated prices this was virtually the same amount as in 2004.Conclusion:  Our results show that the combination of public funding and freedom to establish a practice ensures that services are available for the individuals who are most in need of treatment. The authorities also have control over costs. The experiences from the orthodontic services in Norway are useful for policymakers in other countries. In particular, an important finding is that an orthodontic service where the state subsidy depends on the severity of the malocclusion can secure both equal access to the services and contain costs.
Local Applications of GM‐CSF Induce the Recruitment of Immune Cells in Cervical Low‐Grade Squamous Intraepithelial Lesions
Authors: Hubert Pascale , Doyen Jean , Capelle Xavier , Arafa Mohammad , Renoux Virginie , Bisig Bettina , Seidel Laurence , Evrard Brigitte , Bousarghin Latifa , Gerday Colette , Boniver Jacques , Foidart Jean‐Michel , Delvenne Philippe , Jacobs Nathalie 
Published: March 2010

Citation Hubert P, Doyen J, Capelle X, Arafa M, Renoux V, Bisig B, Seidel L, Evrard B, Bousarghin L, Gerday C, Boniver J, Foidart J‐M, Delvenne P, Jacobs N. Local applications of GM‐CSF induce the recruitment of immune cells in cervical low‐grade squamous intraepithelial lesions. Am J Reprod Immunol 2010; 64: 126–136Problem  Quantitative alterations of antigen‐presenting cells (APC) in (pre)neoplastic lesions of the uterine cervix associated with human papillomavirus (HPV) infection suggest a diminished capacity to capture viral antigens and to induce a protective immune response.Method of study  To test whether a cervical application of GM‐CSF could restore an immune response against HPV in women with cervical low‐grade squamous intraepithelial lesions (LSIL), we performed two clinical trials with 11 healthy women and 15 patients with LSIL.Results  GM‐CSF applications were well tolerated in all enrolled women, and no difference in toxicity between the treated and placebo groups was observed during the follow‐up (until 30 months). Interestingly, in the GM‐CSF treated group, a significant increase of APC and cytotoxic T‐lymphocyte infiltration was observed in the cervical biopsies with no change in regulatory T cell numbers. All the HPV16+ patients exhibited an immune response against HPV16 after GM‐CSF applications, as shown by NK and/or T cells producing IFN‐γ whereas no cellular immune response was observed before the treatment. Moreover, the anti‐virus‐like particles antibody titers also increased after the treatment.Conclusion  These encouraging results obtained from a limited number of subjects justify further study on the therapeutic effect of APC in cervical (pre)neoplastic lesions.
Placental Apoptosis in Health and Disease
Authors: Sharp Andrew N. , Heazell Alexander E.P. , Crocker Ian P. , Mor Gil 
Published: March 2010

Citation Sharp AN, Heazell AEP, Crocker IP, Mor G. Placental apoptosis in health and disease. Am J Reprod Immunol 2010; 64: 159–169Apoptosis, programmed cell death, is an essential feature of normal placental development but is exaggerated in association with placental disease. Placental development relies upon effective implantation and invasion of the maternal decidua by the placental trophoblast. In normal pregnancy, trophoblast apoptosis increases with placental growth and advancing gestation. However, apoptosis is notably exaggerated in the pregnancy complications, hydatidiform mole, pre‐eclampsia, and intrauterine growth restriction (IUGR). Placental apoptosis may be initiated by a variety of stimuli, including hypoxia and oxidative stress. In common with other cell‐types, trophoblast apoptosis follows the extrinsic or intrinsic pathways culminating in the activation of caspases. In contrast, the formation of apoptotic bodies is less clearly identified, but postulated by some to involve the clustering of apoptotic nuclei and liberation of this material into the maternal circulation. In addition to promoting a favorable maternal immune response, the release of this placental‐derived material is thought to provoke the endothelial dysfunction of pre‐eclampsia. Widespread apoptosis of the syncytiotrophoblast may also impair trophoblast function leading to the reduction in nutrient transport seen in IUGR. A clearer understanding of placental apoptosis and its regulation may provide new insights into placental pathologies, potentially suggesting therapeutic targets.
REVIEW ARTICLE: Sex Hormone Regulation of Innate Immunity in the Female Reproductive Tract: The Role of Epithelial Cells in Balancing Reproductive Potential with Protection against Sexually Transmitted Pathogens
Authors: Wira Charles R. , Fahey John V. , Ghosh Mimi , Patel Mickey V. , Hickey Danica K. , Ochiel Daniel O. 
Published: March 2010

Citation Wira CR, Fahey JV, Ghosh M, Patel MV, Hickey DK, Ochiel DO. Sex hormone regulation of innate immunity in the female reproductive tract: the role of epithelial cells in balancing reproductive potential with protection against sexually transmitted pathogens. Am J Reprod Immunol 2010The immune system in the female reproductive tract (FRT) does not mount an attack against HIV or other sexually transmitted infections (STI) with a single endogenously produced microbicide or with a single arm of the immune system. Instead, the body deploys dozens of innate antimicrobials to the secretions of the female reproductive tract. Working together, these antimicrobials along with mucosal antibodies attack many different viral, bacterial and fungal targets. Within the FRT, the unique challenges of protection against sexually transmitted pathogens coupled with the need to sustain the development of an allogeneic fetus have evolved in such a way that sex hormones precisely regulate immune function to accomplish both tasks. The studies presented in this review demonstrate that estradiol and progesterone secreted during the menstrual cycle act both directly and indirectly on epithelial cells and other immune cells in the reproductive tract to modify immune function in a way that is unique to specific sites throughout the FRT. As presented in this review, studies from our laboratory and others demonstrate that the innate immune response is under hormonal control, varies with the stage of the menstrual cycle, and as such is suppressed at mid‐cycle to optimize conditions for successful fertilization and pregnancy. In doing so, a window of STI vulnerability is created during which potential pathogens including HIV enter the reproductive tract to infect host targets.
A conceptual model of plant community changes following cessation of cultivation in semi‐arid grassland
Authors: Wong Nathan K. , Morgan John W. , Dorrough Josh 
Published: March 2010

AbstractQuestion: Can vegetation changes that occur following cessation of cultivation for cereal crop production in semi‐arid native grasslands be described using a conceptual model that explains plant community dynamics following disturbance?Location: Eighteen native grasslands with varying time‐since‐last cultivation across northern Victoria, Australia.Methods: We examined recovery of native grasslands after cessation of cultivation along a space for‐ time chronosequence. By documenting floristic composition and soil properties of grasslands with known cultivation histories, we established a conceptual model of the vegetation states that occur following cessation of cultivation and inferred transition pathways for community recovery.Results: Succession from an exotic‐dominated grassland to native grassland followed a linear trajectory. These changes represent an increase in richness and cover of native forbs, a decrease in cover of exotic annual species and little change in native perennial graminoids and exotic perennial forbs. Using a state‐and‐transition model, two distinct vegetation states were evident: (1) an unstable, recently cultivated state, dominated by exotic annuals, and (2) a more diverse, stable state. The last‐mentioned state can be divided into two further states based on species composition: (1) a never‐cultivated state dominated by native perennial shrubs and grasses, and (2) a long‐uncultivated state dominated by a small number of native perennial and native and exotic annual species that is best described as a subset of the never‐cultivated state. Transitions between these states are hypothesized to be dependent upon landscape context, seed availability and soil recovery.Conclusions: Legacies of past land use on soils and vegetation of semi‐arid grasslands are not as persistent as in other Australian communities. Recovery appears to follow a linear, directional model of post‐disturbance regeneration which may be advanced by overcoming dispersal barriers hypothesised to restrict recovery.
Discovery of an unusual new radio source in the star-forming galaxy M82: faint supernova, supermassive black hole or an extragalactic microquasar?
Authors: Muxlow T. W. B. , Beswick R. J. , Garrington S. T. , Pedlar A. , Fenech D. M. , Argo M. K. , Van Eymeren J. , Ward M. , Zezas A. , Brunthaler A. 
Published: March 2010

Abstract
A faint new radio source has been detected in the nuclear region of the starburst galaxy M82 using Multi-Element Radio-Linked Interferometer Network radio observations designed to monitor the flux density evolution of the recent bright supernova SN2008iz. This new source was initially identified in observations made between 2009 May 1 and 5 but had not been present in observations made 1 week earlier, or in any previous observations of M82. In this Letter, we report the discovery of this new source and monitoring of its evolution over its first 9 months of existence. The true nature of this new source remains unclear, and we discuss whether this source is an unusual and faint supernova, a supermassive black hole associated with the nucleus of M82 or intriguingly the first detection of radio emission from an extragalactic microquasar.