bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet‐dependent accumulation of leukocytes in sinusoids mediates hepatocellular damage in bile duct ligation‐induced cholestasis
Authors: Laschke M W , Dold S , Menger M D , Jeppsson B , Thorlacius H 
Published: November 2007

Background:Although it is well known that extrahepatic cholestasis induces liver damage, the mechanisms are still not completely understood. The aim of the present study was to evaluate the role of platelets and P‐selectin in cholestasis‐induced liver injury.Experimental approach:C57BL/6 mice underwent bile duct ligation (BDL) and pretreatment with an anti‐GP1bα antibody, which depletes platelets, an anti‐P‐selectin antibody or a control antibody. Hepatic platelet and leukocyte recruitment as well as microvascular perfusion were determined by intravital fluorescence microscopy.Key results:BDL caused significant liver damage and sinusoidal perfusion failure. BDL further induced hepatic platelet accumulation with widespread intravascular platelet aggregates, increased platelet adhesion in postsinusoidal venules and massive platelet accumulation in liver sinusoids. Administration of the anti‐GP1bα antibody reduced systemic platelet count by 90%. Depletion of platelets in BDL mice not only abolished accumulation and adhesion of platelets in sinusoids and venules but also restored sinusoidal perfusion and reduced liver enzymes by more than 83%. Platelet depletion further reduced BDL‐associated sinusoidal leukocyte accumulation by 48% although leukocyte–endothelium interactions in venules were not affected. Immunoneutralization of P‐selectin also inhibited hepatic microvascular accumulation of platelets and leukocytes, and protected against cholestasis‐provoked hepatocellular damage.Conclusions and implications:Platelets play an important role in BDL‐induced liver injury by promoting leukocyte recruitment and deteriorating microvascular perfusion. Moreover, our findings demonstrate that cholestasis‐induced accumulation of platelets is mediated by P‐selectin. Thus, targeting platelet accumulation may be a useful strategy against liver damage associated with obstructive jaundice.British Journal of Pharmacology (2008) 153, 148–156; doi:10.1038/sj.bjp.0707578; published online 19 November 2007
The potential and challenges for student teachers' learning of subject‐specific pedagogical knowledge within secondary school subject departments
Authors: Burn Katharine , Childs Ann , McNicholl Jane 
Published: November 2007

This article draws on two research studies concerned with student teachers' learning of subject‐specific pedagogical knowledge: a naturalistic study within two secondary school science departments and a collaborative action research project focused on two contested aspects of the history curriculum. Both confirmed the complexity of the process by which teachers' pedagogical constructions are created and the many components they comprise.The first study revealed rich opportunities for student teachers to observe and engage collaboratively in such processes within subject departments which have a strong geographical location in a team room, and the confidence among staff to admit problems and seek advice. In contrast, the second project's explicit focus on contested aspects of the curriculum saw mentors questioning a critical component of their pedagogical constructions. This inhibited the range of examples they shared with student teachers and their willingness to engage collaboratively with them in creating new ones. Paradoxically, close collaboration between mentors and tutors effectively restricted opportunities to learn from different conceptions of the subject held within the school department.Together the studies raise important questions about the most effective ways of making accessible to student teachers the subject‐specific pedagogical knowledge held across the epistemic communities of subject departments.
Didactics of mathematics: an epistemological approach to mathematics education
Authors: Winsløw Carl 
Published: November 2007

I present some key ideas and examples of (mainly French) work in the didactics of mathematics with the aim of identifying the didactics approach to education in relation to more general approaches. In particular I discuss three crucial features of didactics:

its epistemological character, i.e. the central focus on specific knowledge in different forms, and the conditions for enabling pupils to acquire it;
its relations to the background science (in casu, mathematics as a science);
its actual and potential roles in relation to teaching and teachers (in particular, didactics as a design science and as a part of teachers' education and professional knowledge base).
Marker development for the genetic study of natural variation inArabidopsis thaliana
Authors: Nemri Adnane , Neff Michael M. , Burrell Michael , Jones Jonathan D.G. , Studholme David J. 
Published: November 2007

AbstractSummary: We report AtPRIMER, an application that automates the discovery of new polymorphic markers between ecotypes of Arabidopsis thaliana. On specifying two ecotypes and the genomic region of interest, the script retrieves all corresponding single nucleotide polymorphisms (SNPs) and generates CAPS and/or dCAPS PCR primer sequences. We show that AtPRIMER accurately found specific polymorphic markers for our linkage mapping project. AtPRIMER will therefore be useful for efficient marker development with high density and specificity.Availability: This PERL/CGI program is available for non-commercial users at http://www.AtPRIMER.tsl.ac.uk. The web-based version is available for public use at the same URL.Contact: adnane.nemri@tsl.ac.uk
Partitioning heterotrophic and rhizospheric soil respiration in a mature Douglas-fir (Pseudotsuga menziesii) forest
Authors: Lalonde Rachelle G. , Prescott Cindy E. 
Published: November 2007

Total belowground respiration (Rs) was partitioned into heterotrophic (Rh) and rhizospheric (Rr) respiration to determine the amount of CO2 originating from each component in a coastal Douglas-fir ( Pseudotsuga menziesii (Mirb.) Franco) forest. Rh was measured within cylinders from which roots, hyphae, and associated rhizosphere organisms were excluded by a 0.5 μm nylon mesh and installed 50 cm into the soil. Rs was 12 Mg C·ha–1·year–1 and ranged from 0.71 to 6.57 g C·m–2·day–1 during the 15 month experiment. Rh was 7.8 Mg C·ha–1·year–1, which contributed 65% of Rs, mostly between May and August. Rr was 4.2 Mg C·ha–1·year–1 (35% of Rs) and peaked in spring and fall. Soil temperature described the variability in Rs (p = 0.0004) better than soil moisture (p = 0.6156) and Rh was more closely related to temperature than was Rr. Values of Q10 were 1.7 for Rs and 2.2 for Rh. We also assessed three potential sources of error associated with this root-exclusion technique: respiration from decaying severed roots, stimulated respiration as a result of cylinder installation, and lateral diffusion of CO2 into cylinders. None of these artifacts were found to be significant sources of error in this experiment.
Changes in understory light regime in a beech–maple forest after a severe ice storm
Authors: Arii Ken , Lechowicz Martin J. 
Published: November 2007

We assessed canopy openness (%) in an old-growth beech–maple forest immediately before and in the 3 years following a severe ice storm. We estimated canopy openness using hemispherical photographs taken at a height of 0.6 m above the soil surface in 101 permanent plots. Mean canopy openness increased from a prestorm value of 7.7% to 16.6% in the summer immediately following the storm. However, the mean canopy openness returned to prestorm levels within 3 years. The changes in canopy openness immediately after the storm were significantly influenced by canopy openness prior to the storm and also by species composition; plots with lower canopy openness prior to the storm and plots that consisted of more shade-tolerant species had greater canopy damage. While canopy gaps are often considered to promote the establishment of shade-intolerant species in the deciduous forests of eastern North America, gaps created by ice storms at our study site may not persist long enough to promote the establishment of these species.
Changes in site productivity and the recovery of soil properties following wet- and dry-weather harvesting disturbances in the Atlantic Coastal Plain for a stand of age 10 years
Authors: Eisenbies Mark H. , Burger James A. , Aust W. Michael , Patterson Steven C. 
Published: November 2007

Wet-weather logging can cause severe soil physical disturbances and redistribute residues. Although some research indicates negative effects of such disturbances on individual tree growth, the long-term resilience and resistance of soils and the ameliorative effects of site preparation are not fully understood. Three 20 ha loblolly pine ( Pinus taeda L.) plantations located on fertile wet pine flats on the coastal plain of South Carolina were subjected to five treatment combinations of harvest (wet and dry) and site preparation. Mean tree heights were 10.2–11.5 m, and stand biomass ranged between 95 and 143 Mg/ha. A rank diagnostic indicates that wet-weather harvesting did not significantly change site productivity between rotations, and bedding improved site productivity. At the polypedon scale (0.04 ha), there were no significant differences in tree height, biomass, or the rank diagnostic among classes of soil physical disturbances or harvesting residues when bedding was employed. On nonbedded sites, some levels of disturbance appeared to be superior to minimally disturbed sites. Based on 10 year results, wet pine flats are apparently resistant and resilient to the effects of wet-weather harvesting.
Nitrogen and calcium additions increase forest growth in northeastern USA spruce–fir forests
Authors: Kulmatiski Andrew , Vogt Kristiina A. , Vogt Daniel J. , Wargo Phillip M. , Tilley Joel P. , Siccama Thomas G. , Sigurdardottir Ragnhildur , Ludwig Dirk 
Published: November 2007

We determined responses of red spruce ( Picea rubens Sarg.) – balsam fir ( Abies balsamea (L.) Mill.) forests to 6 years of nitrogen (N), calcium (Ca), and N + Ca treatments (100, 160, and 260 kg·ha–1·year–1of N, Ca, and N + Ca, respectively) in New York (NY) and New Hampshire (NH). Forest responses to Ca treatments were also determined in Vermont (VT). Nitrogen treatments increased aboveground net primary production (ANPP) by 33% and 25% above controls in NY and NH, respectively. Similarly, N + Ca treatments increased ANPP by 27% and 28% in NY and NH, respectively. Calcium treatments increased ANPP by 25% and 21% above controls in NY and VT. Calcium treatment did not increase ANPP in NH, suggesting N, but not Ca limitation. Leaf-litter quantity and quality, and soil C and N storage were greater in treated than in control plots. Fine-root mass and production did not differ among treatments. Trees, therefore, assimilated more soil nutrients without increasing root growth in treated plots. Red spruce ANPP, however, declined or remained unchanged in response to N and Ca additions. The equivalent of 68–102 years of anthropogenic N addition to soils changed forest species composition without decreasing ANPP, and Ca additions did not prevent this change.
Do finer gap mosaics provide a wider niche for Quercus gilva in young Japanese cedar plantations than coarser mosaics? Simulation of spatial heterogeneity of light availability and photosynthetic potentialThis article is one of a selection of papers published in the Special Forum IUFRO 1.05 Uneven-Aged Silvicultural Research Group Conference on Natural Disturbance-Based Silviculture: Managing for Complexity.
Authors: Mizunaga Hiromi 
Published: November 2007

Both the size and the density of gaps affect seedling growth, but these two parameters have a reciprocal relationship at a given gap ratio. The objective of the present study was to clarify the appropriate gap mosaic coarseness required to facilitate the growth of Quercus gilva Blume seedlings in Cryptomeria japonica D. Don plantations. The spatial heterogeneity of the photosynthetic photon flux density on the forest floor was predicted using mimicked hemispherical diagrams under five levels of gap mosaic coarseness ranging from the finest gap mosaic with a gap size of 25 m2 and a gap density of 100·ha–1 to the coarsest mosaic of 400 m2 and 6.25·ha–1. Photosynthetic potentials (PP) were calculated by combining the predicted photosynthetic photon flux density and photosynthetic relationships of Q. gilva and two nontree major competitors ( Mallotus japonicus (Thunb.) Muell. Arg. and Miscanthus sinensis Anderss.). The coarser gap mosaic formed a more heterogeneous and bimodal PP frequency and resulted in a wider site in which the three species had high growth potential without considering competition among species. However, an intermediate mosaic with a gap width to mean canopy height ratio of 0.7 formed the widest realized niche in which Q. gilva would show good growth with a relative PP > 70%, whereas the competitor species would be suppressed with a relative PP < 70%.
Roles of human epidermal growth factor receptor 2, c-jun NH2-terminal kinase, phosphoinositide 3-kinase, and p70 S6 kinase pathways in regulation of cyclin G2 expression in human breast cancer cells
Authors: Le Xiao-Feng , Arachchige-Don Aruni S. , Mao Weiqun , Horne Mary C. , Bast Robert C. 
Published: November 2007

Abstract
The CCNG2 gene that encodes the unconventional cyclin G2 was one of the few genes up-regulated on anti–human epidermal growth factor receptor 2 (HER2) antibody–mediated inhibition of HER2 signaling. The purpose of this study was to explore how HER2 signaling modulates cyclin G2 expression and the effect of elevated cyclin G2 on breast cancer cell growth. Treatment of breast cancer cells that overexpress HER2 (BT474, SKBr3, and MDAMB453) with the anti-HER2 antibody trastuzumab or its precursor 4D5 markedly up-regulated cyclin G2 mRNA in vitro and in vivo, as shown by real-time PCR. Immunoblot and immunofluorescence analysis with specific antibodies against cyclin G2 showed that anti-HER2 antibody significantly increased cyclin G2 protein expression and translocated the protein to the nucleus. Trastuzumab was not able to induce cyclin G2 expression in cells weakly expressing HER2 (MCF7) or in cells that had developed resistance to trastuzumab. Enforced expression of HER2 in T47D and MDAMB435 breast cancer cells reduced cyclin G2 levels. Collectively, these data suggest that HER2-mediated signaling negatively regulates cyclin G2 expression. Inhibition of phosphoinositide 3-kinase (LY294002), c-jun NH2-terminal kinase (SP600125), and mammalian target of rapamycin (mTOR)/p70 S6 kinase (p70S6K; rapamycin) increased cyclin G2 expression. In contrast, treatment with inhibitors of p38 mitogen-activated protein kinase (SB203580), mitogen-activated protein kinase/extracellular signal–regulated kinase kinase 1/2 (U0126), or phospholipase Cγ (U73122) did not affect cyclin G2 expression. Anti-HER2 antibody in combination with LY294002, rapamycin, or SP600125 induced greater cyclin G2 expression than either agent alone. Ectopic expression of cyclin G2 inhibited cyclin-dependent kinase 2 activity, Rb phosphorylation, cell cycle progression, and cellular proliferation without affecting p27Kip1 expression. Thus, cyclin G2 expression is modulated by HER2 signaling through multiple pathways including phosphoinositide 3-kinase, c-jun NH2-terminal kinase, and mTOR signaling. The negative effects of cyclin G2 on cell cycle and cell proliferation, which occur without altering p27Kip1 levels, may contribute to the ability of trastuzumab to inhibit breast cancer cell growth. [Mol Cancer Ther 2007;6(11):2843–57]
Glycosaminoglycans and their synthetic mimetics inhibit RANTES-induced migration and invasion of human hepatoma cells
Authors: Sutton Angela , Friand Veronique , Papy-Garcia Dulce , Dagouassat Maylis , Martin Loïc , Vassy Roger , Haddad Oualid , Sainte-Catherine Odile , Kraemer Michel , Saffar Line , Perret Gerard Yves , Courty Jose , Gattegno Liliane , Charnaux Nathalie 
Published: November 2007

Abstract
The CC-chemokine regulated on activation, normal T-cell expressed, and presumably secreted (RANTES)/CCL5 mediates its biological activities through activation of G protein–coupled receptors, CCR1, CCR3, or CCR5, and binds to glycosaminoglycans. This study was undertaken to investigate whether this chemokine is involved in hepatoma cell migration or invasion and to modulate these effects in vitro by the use of glycosaminoglycan mimetics. We show that the human hepatoma Huh7 and Hep3B cells express RANTES/CCL5 G protein–coupled receptor CCR1 but not CCR3 nor CCR5. RANTES/CCL5 binding to these cells depends on CCR1 and glycosaminoglycans. Moreover, RANTES/CCL5 strongly stimulates the migration and the invasion of Huh7 cells and to a lesser extent that of Hep3B cells. RANTES/CCL5 also stimulates the tyrosine phosphorylation of focal adhesion kinase and activates matrix metalloproteinase-9 in Huh7 hepatoma cells, resulting in increased invasion of these cells. The fact that RANTES/CCL5-induced migration and invasion of Huh7 cells are both strongly inhibited by anti-CCR1 antibodies and heparin, as well as by β-d-xyloside treatment of the cells, suggests that CCR1 and glycosaminoglycans are involved in these events. We then show by surface plasmon resonance that synthetic glycosaminoglycan mimetics, OTR4120 or OTR4131, directly bind to RANTES/CCL5. The preincubation of the chemokine with each of these mimetics strongly inhibited RANTES-induced migration and invasion of Huh7 cells. Therefore, targeting the RANTES-glycosaminoglycan interaction could be a new therapeutic approach for human hepatocellular carcinoma. [Mol Cancer Ther 2007;6(11):2948–58]
Bevacizumab and rapamycin inhibit tumor growth in peritoneal model of human ovarian cancer
Authors: Huynh Hung , Teo Ching Ching Melissa , Soo Khee Chee 
Published: November 2007

AbstractOvarian cancer is the leading cause of death from gynecologic cancer. Often, the disease has spread beyond the ovary to involve the peritoneal cavity and causes ascites. Whereas mammalian target of rapamycin (mTOR) functions to regulate protein translation, cell cycle progression, and metastasis, vascular endothelial growth factor promotes tumor angiogenesis, ascites formation, and metastasis in ovarian cancer. In this study, an i.p. model of human ovarian cancer was used to determine the antitumor activity of rapamycin, bevacizumab, and rapamycin plus bevacizumab (BEV/RAPA). We report that administration of rapamycin, bevacizumab, and BEV/RAPA in mice bearing peritoneal OV-90 ovarian carcinoma resulted in 74.6%, 82.4%, and 93.3% reduction in i.p. tumor burden, respectively. BEV/RAPA-induced reduction in microvessel density and inhibition of cell proliferation were associated with significant reduction in hypoxia-inducible factor-1α and cyclin D1 and inactivation of downstream targets of mTOR, p70S6 kinase, S6R, and 4E-binding protein 1. BEV/RAPA treatment was not only able to prolong life of i.p. mice but also more effective than rapamycin and bevacizumab to prevent the development of peritoneal carcinomatosis in adjuvant setting and reverse ascites accumulation in heavy peritoneal disease. Our data indicate that simultaneous inhibition of the vascular endothelial growth factor receptor and mTOR pathways with BEV/RAPA or their analogues may represent a novel approach for prevention of metastasis, recurrence, and treatment of ovarian cancer. [Mol Cancer Ther 2007;6(11):2959–66]
Nonimmunosuppressive chemotherapy: EM011-treated mice mount normal T-cell responses to an acute lymphocytic choriomeningitis virus infection
Authors: Aneja Ritu , Kalia Vandana , Ahmed Rafi , Joshi Harish C. 
Published: November 2007

AbstractMyelosuppression and associated immunosuppression are major problems in cancer chemotherapy. Thus, infection remains a significant source of morbidity and mortality during chemotherapy of cancer patients. Viral infections, particularly herpes simplex virus, varicella zoster virus, and cytomegalovirus, result either due to reactivation of latent viruses or new infections as sequelae of chemotherapy and debilitated cell-mediated immunity. Ultimately, the resolution of these infections can only be achieved after the control of malignancy and regaining the patient's ability to mount adequate immune responses. We show here that EM011, a tubulin-binding, nontoxic, orally available anticancer agent, does not alter absolute CD4+, CD8+, B220+, and NK1.1+ cell counts in immunocompetent mice. More importantly, EM011 treatment at tumor-suppressive dosages (300 mg/kg) does not suppress cell-mediated immune responses in mice experimentally challenged with acute lymphocytic choriomeningitis virus infection, in that mice mount robust virus-specific CD8+ and CD4+ T-cell immune responses while maintained on daily drug treatment. Thus, CD8+ and CD4+ T-cell expansion and acquisition of effector functions is not perturbed by EM011 treatment. These data provide compelling evidence to support the nonimmunosuppressive nature of EM011 therapy and provide strong impetus for combining chemotherapy with immunotherapy as a novel anticancer strategy. [Mol Cancer Ther 2007;6(11):2891–9]
Effects of folate and folylpolyglutamyl synthase modulation on chemosensitivity of breast cancer cells
Authors: Cho Robert C. , Cole Peter D. , Sohn Kyoung-Jin , Gaisano Gregory , Croxford Ruth , Kamen Barton A. , Kim Young-In 
Published: November 2007

AbstractFolylpolyglutamyl synthase (FPGS) converts intracellular folates and antifolates to polyglutamates. Polyglutamylated folates and antifolates are retained in cells longer and are better substrates than their monoglutamate counterparts for enzymes involved in one-carbon transfer. FPGS modulation affects the chemosensitivity of cancer cells to antifolates, such as methotrexate, and 5-fluorouracil (5FU) by altering polyglutamylation of antifolates and specific target intracellular folate cofactors. However, this effect may be counterbalanced by FPGS modulation-induced changes in polyglutamylation of other intracellular folate cofactors and total intracellular folate pools. We generated an in vitro model of FPGS overexpression and inhibition in breast cancer cells by stably transfecting human MDA-MB-435 breast cancer cells with the sense FPGS cDNA or FPGS-targeted small interfering RNA, respectively, and investigated the effects of FPGS modulation on chemosensitivity to 5FU and methotrexate. FPGS modulation-induced changes in polyglutamylation of both antifolates and folate cofactors and in intracellular folate pools affected chemosensitivity of breast cancer cells to pemetrexed and trimetrexate whose cytotoxic effects do or do not depend on polyglutamylation, respectively, in a predictable manner. However, the effects of FPGS modulation on the chemosensitivity of breast cancer cells to 5FU and methotrexate seem to be highly complex and depend not only on polyglutamylation of a specific target intracellular folate cofactor or methotrexate, respectively, but also on total intracellular folate pools and polyglutamylation of other intracellular folate cofactors. Whether or not FPGS modulation may be an important clinical determinant of chemosensitivity of breast cancer cells to 5FU and methotrexate-based chemotherapy needs further exploration. [Mol Cancer Ther 2007;6(11):2909–20]