bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms underlying fibronectin‐induced up‐regulation of P2X4R expression in microglia: distinct roles of PI3K–Akt and MEK–ERK signalling pathways
Authors: Tsuda Makoto , Toyomitsu Emika , Kometani Miho , Tozaki‐Saitoh Hidetoshi , Inoue Kazuhide 
Published: February 2009

AbstractMicroglia are resident immune cells in the central nervous system that become activated and produce pro‐inflammatory and neurotrophic factors upon activation of various cell‐surface receptors. The P2X4 receptor (P2X4R) is a sub‐type of the purinergic ion‐channel receptors expressed in microglia. P2X4R expression is up‐regulated under inflammatory or neurodegenerative conditions, and this up‐regulation is implicated in disease pathology. However, the molecular mechanism underlying up‐regulation of P2X4R in microglia remains unknown. In the present study, we investigated the intracellular signal transduction pathway that promotes P2X4R expression in microglia in response to fibronectin, an extracellular matrix protein that has previously been shown to stimulate P2X4R expression. We found that in fibronectin‐stimulated microglia, activation of phosphatidylinositol 3‐kinase (PI3K)–Akt and mitogen‐activated protein kinase kinase (MAPK kinase, MEK)–extracellular signal‐regulated kinase (ERK) signalling cascades occurred divergently downstream of Src‐family kinases (SFKs). Pharmacological interference of PI3K–Akt signalling inhibited fibronectin‐induced P2X4R gene expression. Activation of PI3K–Akt signalling resulted in a decrease in the protein level of the transcription factor p53 via mouse double minute 2 (MDM2), an effect that was prevented by MG‐132, an inhibitor of the proteasome. In microglia pre‐treated with MG‐132, fibronectin failed to up‐regulate P2X4R expression. Conversely, an inhibitor of p53 caused increased expression of P2X4R, implying a negative regulatory role of p53. On the other hand, inhibiting MEK–ERK signalling activated by fibronectin suppressed an increase in P2X4R protein but interestingly did not affect the level of P2X4R mRNA. We also found that fibronectin stimulation resulted in the activation of the translational factor eIF4E via MAPK‐interacting protein kinase‐1 (MNK1) in an MEK–ERK signalling‐dependent manner, and an MNK1 inhibitor attenuated the increase in P2X4R protein. Together, these results suggest that the PI3K–Akt and MEK–ERK signalling cascades have distinct roles in the up‐regulation of P2X4R expression in microglia at transcriptional and post‐transcriptional levels, respectively.
Functional characterization and pharmacological rescue of melanocortin‐4 receptor mutations identified from obese patients
Authors: Fan Zhen‐Chuan , Tao Ya‐Xiong 
Published: February 2009

AbstractAs the most common monogenic form of human obesity, about 130 naturally occurring melanocortin‐4 receptor (MC4R) gene mutations have been identified. In this study, we reported detailed functional characterization of 10 novel human MC4R (hMC4R) mutants including R7C, C84R, S127L, S136F, W174C, A219V, P230L, F261S, I317V and L325F. Flow cytometry experiments showed that six mutants, including R7C, C84R, S127L, W174C, P230L and F261S, have decreased cell surface expression. The other four mutants are expressed at similar levels as the wild‐type hMC4R. Binding assays showed that the mutants have similar binding affinities for the agonist and endogenous antagonist agouti‐related protein. Signalling assays showed that S136F is defective in signalling. Multiple mutagenesis showed that S136 of hMC4R is required for the normal function of the receptor. To identify potential therapeutic approaches for patients with intracellularly retained MC4R mutants, we tested the effect of an MC4R inverse agonist, ML00253764, on C84R and W174C. We showed that ML00253764 could function as a pharmacological chaperone rescuing the mutant MC4Rs to the cell surface. The rescued mutants are functional with increased cAMP production in response to agonist stimulation. In conclusion, of 10 mutants we studied, 6 had decreased cell surface expression. Pharmacological chaperone is a potential approach for treating obesity caused by MC4R mutations that result in intracellular retention.
p27Kip1 as a prognostic factor in breast cancer: a systematic review and meta‐analysis
Authors: Guan Xiaoxiang , Wang Yucai , Xie Ruilian , Chen Longbang , Bai Jianling , Lu Jia , Kuo Macus Tien 
Published: February 2009

AbstractThe aim of this study was to comprehensively evaluate via a meta‐analysis the association between p27 expression and clinical outcome in breast cancer patients. We conducted a meta‐analysis of 20 studies (n= 6463 patients) that evaluated the correlation between p27 expression and indicators of breast cancer clinical outcome, including overall survival (OS), disease‐free survival (DFS) and relapse‐free survival (RFS). Data pooling was performed by RevMan 4.2. A total of 60% (9 of 15) of the studies showed a significant association between p27 high expression and OS, whereas 25% (2 of 8) and 60% (3 of 5) studies demonstrated a correlation between p27 high expression and DFS and RFS, respectively. The relative risks (RRs) were 1.34 (1.26–1.42) for OS (P < 0.00001), 1.27 (1.10–1.47) for DFS (P= 0.001) and 1.49 (0.92–2.42) for RFS (P= 0.10). In lymph node‐negative breast cancer patients, the RRs for OS and RFS were 1.84 (1.30–2.59; P= 0.0005) and 1.30 (0.20–8.50; P= 0.78), respectively. In lymph node‐positive breast cancer patients, the RRs for OS and RFS were 2.99 (1.77–5.07; P < 0.0001) and 1.49 (0.80–2.77; P= 0.21), respectively. This meta‐analysis indicates that reduced p27 is an independent prognostic factor for poor overall and disease‐free cancer survival.
Assessing the dominance of Phleum pratense cv. climax, a species commonly used for ski trail restoration
Authors: Isselin‐Nondedeu Francis , Bédécarrats Alain 
Published: February 2009

AbstractQuestions: (1) Are some species used for ski trail restoration too dominant to allow native species to re‐establish? (2) What plant traits can be used to predict which species are good competitors? We tested the hypothesis that limited native species establishment on ski trails is caused by (1) the dominance of Phleum pratense cv. climax (PPC) and (2) the asymmetry of competitive interactions.Location: Sub‐alpine area in the northern French Alps.Methods: PPC was cultivated outdoors over 2 years with 15 alpine species in a systematic design with high‐ and low‐nutrient soil conditions. For each species relative survival, competitive performance and relationships with plant traits were measured.Results: PPC exerted strong dominance on most of its neighbouring species. Survival performance of Anthyllis vulneraria, Luzula sudetica and Lotus alpinus were dramatically reduced. Results of above‐ground competition showed that species were trapped in asymmetric competition. Festuca rubra, Trifolium repens, Alchemilla xanthochlora, Trifolium pratense and Plantago alpina best counteracted PPC. Below‐ground competition was more symmetric, particularly at the high nutrient level. Plant traits such as biomass, canopy size and specific leaf area were positively correlated with competitive performance of the species.Conclusion: The study has implications for the management of restored ski trails since PPC may hinder the establishment of native sub‐alpine species. Consequently, recommendations should focus on (1) maintaining a low proportion or decreasing the proportion of PPC seeds in the revegetation mix and (2) reducing soil fertilization. Plant traits and competition experiments can help to predict changes in restored grasslands.
Automobility and the Geographies of the Car
Authors: Merriman Peter 
Published: February 2009

AbstractThe motor car or automobile has had a profound impact on global mobility, settlement patterns, the global economy, and the environment. Transport policy‐makers and environmentalists highlight the unsustainable nature of contemporary petrol‐car usage, yet despite widespread calls to rethink contemporary automobility and move towards more sustainable forms of public and private travel, it is only in recent years that social scientists have started to examine the social and cultural geography of the motor car, driving and the spaces of the street, road and motorway in any depth. In this article, I outline some of the research which has been undertaken on the geographies and sociologies of the spaces and practices of driving, focusing in particular on the UK. First, the article outlines the major impact the motor car has had on the geographies of road space. It examines how motor roads have shaped our experience of space and place, and outlines studies of their design, inhabitation, and regulation. Second, this article discusses embodied inhabitations of the spaces of the car: how motor cars have been consumed; how they have shaped our embodied apprehensions of our surroundings; and how they facilitate social and cultural relations. Finally, this article concludes by examining the innovative methods which are increasingly being utilised and developed by social scientists to explore the socialities of automotive spaces.
Morpho‐Physiologic Characteristics of Dorsal Subicular Network in Mice after Pilocarpine‐Induced Status Epilepticus
Authors: He De Fu , Ma Dong Liang , Tang Yong Cheng , Engel Jr Jerome , Bragin Anatol , Tang Feng Ru 
Published: February 2009

AbstractThe goal of this study was to examine the morpho‐physiologic changes in the dorsal subiculum network in the mouse model of temporal lobe epilepsy using extracellular recording, juxtacellular and immunofluorescence double labeling, and anterograde tracing methods. A significant loss of total dorsal subicular neurons, particularly calbindin, parvalbumin (PV) and immunopositive interneurons, was found at 2 months after pilocarpine‐induced status epilepticus (SE). However, the sprouting of axons from lateral entorhinal cortex (LEnt) was observed to contact with surviving subicular neurons. These neurons had two predominant discharge patterns: bursting and fast irregular discharges. The bursting neurons were mainly pyramidal cells, and their dendritic spine density and bursting discharge rates were increased significantly in SE mice compared with the control group. Fast irregular discharge neurons were PV‐immunopositive interneurons and had less dendritic spines in SE mice when compared with the control mice. When LEnt was stimulated, bursting and fast irregular discharge neurons had much shorter latency and stronger excitatory response in SE mice compared with the control group. Our results illustrate that morpho‐physiologic changes in the dorsal subiculum could be part of a multilevel pathologic network that occurs simultaneously in many brain areas to contribute to the generation of epileptiform activity.
Clinical and hematological study for Parvovirus b19 infection in children with acute leukemia
Authors: ZAKI M. E. S. , ASHRAY R. E. 
Published: February 2009

SummaryThe role of Parvovirus B19 in acute leukemia is under debate. This study aimed to detect parvovirus B19 DNA together with its antibodies in the sera of children with recent acute leukemia and those with acute leukemia receiving chemotherapy to clarify the contribution of this infection to changes observed in hematological and clinical presentations in these populations. Two groups were included: Group I comprised 45 children with acute leukemia receiving chemotherapy and Group II comprised 40 children with recently diagnosed acute leukemia. Serum parvovirus B19 IgG and IgM were investigated by enzyme‐linked immunosorbant assay and the virus DNA was sought by polymerase chain reaction assay. Viral DNA was found in 22.2% of Group I patients and in 45% of Group II patients. Hemoglobin levels were significantly reduced in patients with recent infection, accompanied by statistically significant lymphocytosis in Group I patients. Group II patients with recent infection had marked neutropenia with lymphocytosis and thrombocytopenia. There was statistically significant lymphadenopathy and hepatosplenomegaly in patients with recent infection in both groups. Parvovirus B19 infection is an important cause of cytopenia in children with acute leukemia both when recently diagnosed and receiving chemotherapy. This can affect the schedule of chemotherapy. Moreover, the presence of Parvovirus B19 is associated with marked lymphadenopathy and hepatosplenomegaly.
Intrafloral differentiation of stamens in heterantherous flowers
Authors: LUO Zhong‐Lai , GU Lei , ZHANG Dian‐Xiang 
Published: February 2009

AbstractFlowers that have heteromorphic stamens (heterantherous flowers) have intrigued many researchers ever since the phenomenon was discovered in the 19th century. The morphological differentiation in androecia has been suggested as a reflection of “labor division” in pollination in which one type of stamens attracts pollinators and satisfies their demand for pollen as food and the other satisfies the plant's need for safe gamete dispersal. The extent and patterns of stamen differentiation differ notably among taxa with heterantherous flowers. Seven species with heteromorphic stamens in three genera were sampled from Leguminosae and Melastomataceae, and the morphological difference of androecia, pollen content, pollen histochemistry and viability, pollen micro‐morphology, as well as the main pollinators were examined and compared. Pollen number differs significantly between stamen sets of the same flower in most species investigated, and a correlation of pollen number and anther size was substantiated. Higher pollen viabilities were found in the long (pollinating) stamens of Senna alata (L.) Roxb. and S. bicapsularis (L.) Roxb. Dimorphic pollen exine ornamentation is reported here for the first time in Fordiophyton faberi Stapf. The height of stigma and anther tips of the long stamens in natural conditions was proved to be highly correlated, supporting the hypothesis that they contact similar areas of the pollinator's body.
Mating system and genetic diversity of a rare desert legume Ammopiptanthus nanus (Leguminosae)
Authors: CHEN Guo‐Qing , HUANG Hong‐Wen , CRAWFORD Daniel J , PAN Bo‐Rong , GE Xue‐Jun 
Published: February 2009

Abstract Ammopiptanthus nanus is an endangered evergreen shrub endemic to the deserts of central Asia and plays an important role in delaying further desertification. We examined allozyme variation and AFLP diversity in A. nanus populations and investigated the mating system of this species using progeny arrays assayed for polymorphic allozyme loci. Mating system analysis in the Keyi'eryongke'er population showed low levels of out‐crossing, and strong inbreeding depression. Low levels of genetic variation were detected at both population (allozyme, Pp= 14.0%, A= 1.14, He= 0.031; AFLP, Pp= 14.5%, Shannon's information index I= 0.063) and species (allozyme, Pp= 21.1%, A= 1.21, He= 0.040; AFLP, Pp= 20.9%, I= 0.083) levels; while moderate genetic differentiation existed among populations, as indicated by allozymes (GST= 0.081) and AFLP (GST= 0.151–0.193). Founder effect, bottlenecks in evolutionary history, the mixed mating system and co‐ancestry may have influenced the level of genetic diversity in A. nanus. Markers of both types provide new insights for conservation management, indicating that the Biao'ertuokuoyi and Keyi'eryongke'er populations should be given priority for in situ conservation and regarded as seed sources for ex situ conservation.
New mechanism of transforming growth factor‐β signaling in hepatoma: Dramatic up‐regulation of tumor initiating cells and epidermal growth factor receptor expression
Authors: Nishimura Takeshi , Azuma Toshifumi , Yokoyama Akiko , Ochiai Hiromi , Saito Hidetsugu , Hibi Toshifumi 
Published: February 2009

Aim:  Transforming growth factor‐β (TGF‐β) has dual activity in tumor cells. We studied the effect of TGF‐β on tumor‐initiating cells (TICs), which are similar in self‐renewal and differentiation features to normal adult stem cells.Methods:  We used side population (SP) cells that exclude DNA binding dye Hoechst 33342 to obtain TICs, studied the differences in the kinetics of the SP cell response to TGF‐β treatment between hepatic tumor cell lines, and performed gene analysis.Results:  SP cells from all cell lines have higher proliferative ability compared to non‐SP cells and they are drug resistant. TGF‐β treatment increased the percentage of SP cells (%SP) and the survival rate; chemotherapeutic drug resistance developed only in K‐251 SP cells. Gene analysis showed that TGF‐β up‐regulated epidermal growth factor receptor (EGFR) only in K‐251 cells. There were no EGFR mutations in K‐251, which had been reported in lung cancer. Knockdown of Smad4 using the small‐interfering RNA technique in K‐251 cells inhibited EGFR overexpression and significantly decreased the %SP. In contrast, the JNK inhibitor had little effect on EGFR expression or the %SP.Conclusion:  TGF‐β treatment of K‐251 cells causes tumor progression and the anti‐cancer drug resistant phenotype by increasing SP.
Effect of bile acids on the biliary excretion of pravastatin in rats
Authors: Morisawa Yoshihiko , Takikawa Hajime 
Published: February 2009

Aim:  The biliary excretion of pravastatin, an HMG‐CoA reductase inhibitor, is mediated by the multidrug resistance protein 2, but a recent report suggests that pravastatin is also a substrate of the bile salt export pump, which transports bile acids. We examined the effects of bile acids on biliary pravastatin excretion in rats.Methods:  The effect of taurocholate on biliary pravastatin excretion, and that of pravastatin on biliary taurocholate excretion was examined in bile‐drained rats.Results:  Taurocholate had no effect on biliary pravastatin excretion, whereas pravastatin with a dose to cause biliary excretory maximum significantly inhibited biliary taurocholate excretion.Conclusion:  These data indicate that increased serum bile acids will not affect the pharmacokinetics of pravastatin in patients with hepatobiliary diseases. Although pravastatin inhibited biliary taurocholate excretion, it is unlikely that pravastatin significantly inhibits biliary bile acid excretion by its therapeutic doses.
Source of transmission in children with chronic hepatitis B infection after the implementation of a strategy for prevention in those at high risk
Authors: Komatsu Haruki , Inui Ayano , Sogo Tsuyoshi , Hiejima Eitaro , Kudo Naoko , Fujisawa Tomoo 
Published: February 2009

Aim:  In order to clarify the sources of chronic HBV (hepatitis B virus) infection in children after the implementation of an “at‐risk” strategy in Japan, chronically infected children were assessed. In addition, chronically infected children born to HBsAg‐negative mothers and their family members were assessed to identify the sources of HBV transmission.Methods:  Fifty‐seven children who tested HBsAg‐positive after the initiation of a mother‐to‐child transmission prevention program were enrolled in this study. The full‐genome HBV DNA sequence was analyzed to confirm the transmission sources.Results:  Of the 57 patients, 37 (65%) were born to HBV carrier mothers. The remaining 20 (35%) patients were born to HBsAg‐negative mothers. Fourteen of these patients had HBV carrier fathers, and 2 patients, who were siblings, did not have an HBV carrier father. The remaining 4 patients had no family members with HBV infection. Phylogenetic tree analysis confirmed that father‐to‐child transmission and sibling‐to‐sibling transmission occurred in 3 families and 1 family, respectively.Conclusion:  Although vaccine failure of mother‐to‐child transmission was the major cause of chronic HBV infection in children, father‐to‐child transmission was the second most common mode of transmission. In addition, sibling‐to‐sibling transmission was found. Unless at‐risk individuals and groups can be accurately identified to prevent horizontal transmission, the introduction of universal vaccination is essential for achieving the elimination of HBV infection in Japan.
Impaired regulation of serum hepcidin during phlebotomy in patients with chronic hepatitis C
Authors: Sugimoto Ryosuke , Fujita Naoki , Tomosugi Naohisa , Hara Nagisa , Miyachi Hirohide , Tanaka Hideaki , Takeo Masaki , Nakagawa Naoki , Iwasa Motoh , Kobayashi Yoshinao , Kaito Masahiko , Takei Yoshiyuki 
Published: February 2009

Aim:  This study was conducted to determine the clinical relevance of hepcidin, a recently identified key iron regulatory hormone, in patients with chronic hepatitis C virus (C‐HCV).Methods:  Serum hepcidin levels were measured in 9 C‐HCV patients by surface‐enhanced laser desorption/ionization time of flight mass spectrometry (SELDI‐TOF‐MS), and compared to those of healthy controls. Sequential changes of hepcidin were also investigated during phlebotomy.Results:  Serum hepcidin and ferritin were significantly higher in C‐HCV than in controls (P = 0.0002), these two variables were strongly related to each other (r = 0.658; P < 0.01), and phlebotomy significantly decreased serum hepcidin in C‐HCV (P = 0.0007); all these results recollect the hepcidin response to iron signal. Hepcidin/ferritin ratio, an index of the appropriateness of hepcidin expression relative to iron overload, was significantly lower in C‐HCV than in controls (0.33 ± 0.41 vs. 0.73 ± 0.36, P = 0.0068). This relative impairment of hepcidin expression was not reversible after phlebotomy (P = NS).Conclusions:  Although the hepcidin expression responds to iron conditions in C‐HCV, this response is relatively limited. This relative impairment of hepcidin expression may be relevant to disease progression, and thus correction of its regulation may be beneficial for these iron‐overloaded C‐HCV patients.
Liver stiffness measured by transient elastography correlates with fibrosis area in liver biopsy in patients with chronic hepatitis C
Authors: Nitta Yoshifumi , Kawabe Naoto , Hashimoto Senju , Harata Masao , Komura Naruomi , Kobayashi Kyoko , Arima Yuko , Shimazaki Hiroaki , Nakano Takuji , Murao Michihito , Ichino Naohiro , Osakabe Keisuke , Aoki Hisako , Hosoe Yoko , Sugiyama Hiroko , Nishikawa Toru , Yoshioka Kentaro 
Published: February 2009

Aim:  Liver stiffness (LS) measured by transient elastography (TE) has been reported to correlate with liver fibrosis, which is usually semiquantitatively assessed. In the present study, the fibrosis area was measured by image analysis software in liver biopsy specimens and its correlation with LS was assessed.Methods:  LS was measured by TE in all 165 patients with chronic hepatitis C virus (HCV) infection who underwent liver biopsy consecutively in Fujita Health University Hospital from July 2004 to September 2007.Results:  Fibrosis area was significantly correlated with fibrosis stage as assessed by the Metavir score (ρ = 0.733, P < 0.0001). The optimal cut‐off value of fibrosis area was 1.6% for F > or = 2, 3.1% for F > or = 3, and 3.8–6.4% for F4. LS was significantly correlated with fibrosis stage (ρ = 0.734, P < 0.0001). The optimal cut‐off value of LS was 7.1 kPa for F > or = 2, 9.6 kPa for F > or = 3 and 11.6–16.9 kPa for F4. Multiple linear regression analysis selected fibrosis area (P = 0.0002), alanine aminotransferase (ALT) (P = 0.0237), γ‐glutamyltransferase (γ‐GTP) (P = 0.0114), prothrombin time (P = 0.0114) and hyaluronic acid (P < 0.0001) as factors correlating with LS.Conclusion:  The correlation between LS and liver fibrosis was confirmed by the objective measurement of fibrosis area. ALT was significantly correlated with LS, suggesting that inflammatory activity also affects LS values. Despite some limitation, LS measurement is a useful method for the diagnosis of liver fibrosis.