bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of elevated CO2 on carbohydrate and ureide concentrations in soybean inoculated with different strains of Bradyrhizobium japonicum
Authors: Bertrand Annick , Prévost Danielle , Juge Christine , Chalifour François-P. 
Published: August 2011

Elevated CO2 increases soybean growth and photosynthesis, and the resulting additional supply of photosynthates stimulates nodule activity. To characterize its biochemical response to both CO2 and bradyrhizobial strains, soybean inoculated with three strains of Bradyrhizobium japonicum was grown in growth chambers under ambient (400 µmol·mol–1) or elevated (800 µmol·mol–1) CO2. Soluble sugars were generally more abundant in leaves and nodules under elevated CO2, while starch and pinitol were depleted, indicating that additional photosynthates were rapidly used, in particular for nodule growth (dry mass increased by 65%). Ureides (allantoin and allantoic acid) increased under elevated CO2 in leaves, while this increase was not significant in nodules. The indigenous strain 12NS14 induced the highest ureides concentration in nodules under elevated CO2 along with the highest nitrogenase activity and increase in shoot dry mass, indicating a positive-feedback stimulation: soybean mobilized energy reserves to support more nodules, and in return nodules synthesized more ureides to support plant growth. In contrast, the commercial strain 532c resulted in the highest ureide concentrations in leaves, coupled with the lowest nitrogenase activity and nodules yield, suggesting a feedback inhibition of nodule activity. Our results show that selection of B. japonicum strains better adapted to elevated CO2 could improve soybean performance.
Natural plant colonization of borrow pits in boreal forest highlands of eastern Canada
Authors: Hugron Sandrine , Andersen Roxane , Poulin Monique , Rochefort Line 
Published: August 2011

Plant colonization after gravel extraction for road construction is slow and is often considered to be primary succession. The goal of this study was to identify the plant communities that spontaneously colonized borrow pits located in boreal climate zones and to assess how environmental variables influenced this colonization process. It also helped identifying potential combinations of plants to use as well as environmental factors to improve to restore borrow pits. A total of 505 plots were inventoried in 117 borrow pits located in the boreal forest highlands 120 km northeast of Quebec City, Quebec, Canada (Parc national des Grands Jardins). Species cover was visually estimated for different plant communities within each borrow pit where slope and soil characteristics were also evaluated. We used multivariate analyses, including clustering, redundancy, and regression tree analyses. The borrow pits studied were undergoing primary succession processes decades after abandonment. The main pioneer species were bryophytes and lichens. Soil water content and soil physicochemistry had the greatest influence on the natural colonization of borrow pits. We observed that, based on the prevailing conditions, the bryophytes Polytrichum piliferum Hedw. and Niphotrichum canescens (Hedw.) Bednarek-Ochyra & Ochyra, lichens of the genus Stereocaulon , and the lichen Trapeliopsis granulosa (Hoffm.) Lumbsch could potentially act as nurse species and could initiate the restoration of borrow pits located in boreal forests.
Quartz arenites of the Cambro-Ordovician Kamouraska Formation, Quebec Appalachians, Canada: I. Deep-water depositional processes in a continental-slope environment
Authors: Malhame Pierre , Hesse Reinhard 
Published: August 2011

The Kamouraska Formation is an uppermost Cambrian – lowermost Ordovician quartz-arenite-dominated unit of controversial origin deposited on the southeastern slope of Laurentia bordering the Iapetus Ocean. It is exposed in the Quebec Appalachians on the south shore of the St. Lawrence Estuary. The formation consists of basal polymictic conglomerate and overlying massive sheet-like quartz arenite. The conglomerate beds are reversely and reversely to normally graded. The quartz arenite beds are generally massive, although they may show coarse-tail grading. Beds containing full or partial Bouma sequences are rare. Paleoflow directions from ripple-cross lamination, ripple marks on bed surfaces, and sole marks point towards southeast, south, and southwest. The clastic sediments of the Kamouraska were transported into the deep sea by sediment gravity flows that evolved from hyperconcentrated to concentrated density flows, and then to turbidity currents. The depositional environment is interpreted to have been a southwest-trending meandering submarine canyon. The exposed part of the canyon deposits is slightly oblique to the strike of slope. If correct, our interpretation establishes the preservation of continental-slope deposits in more distal deep-water siliciclastic sedimentary rocks of the Taconian orogen in Quebec, which traditionally have been interpreted as submarine-fan and (or) basin-plain deposits. The orientation of a canyon near parallel-to strike of the slope may have been controlled by syn-depositional growth faults. The coarsest hyperconcentrated flows, which deposited the conglomerate, were restricted to the deepest parts of the canyon during its early stages of development, whereas the concentrated density flows that deposited the massive quartz-arenite beds covered a wider area.
Geological and depositional setting of the Sirius Passet Lagerstätte (Early Cambrian), North Greenland
Authors: Ineson Jon R. , Peel John S. 
Published: August 2011

The Early Cambrian Sirius Passet Lagerstätte of North Greenland occurs in marine mudstones (Buen Formation) deposited in a slope environment along the eroded scarp of a pre-existing carbonate platform. The shallow-water platform is represented by dolostones of the Portfjeld Formation (Neoproterozoic – earliest Cambrian), which record a belt of tide-swept subtidal ooid shoals and microbial patch reefs at the outer edge of the platform. Solution features and meteoric cements attest to exposure of the platform, accompanied by fracturing, mass wastage and erosional retreat of the escarpment producing slope talus, and extensive debris sheets and olistoliths in basinal deposits. The marine mud-dominated siliciclastics of the Buen Formation, deposited in slope and shelf environments, record the transgression and onlap of the degraded platform in the Early Cambrian. The Sirius Passet Lagerstätte has yielded an arthropod-dominated fossil assemblage of over 40 species, many showing exceptional preservation of soft tissues; the finely laminated mudstones hosting this fauna accumulated from suspension in a poorly oxygenated slope sub-environment, such as an erosional embayment or abandoned slope gully. Although taphonomic features suggest that the fauna is mainly parautochthonous, some components (e.g., sponges, worms, the halkieriids and certain sightless arthropods) may be truly autochthonous. Comparison of the Sirius Passet locality with the renowned Middle Cambrian Burgess Shale of western Canada reveals similarities in overall depositional and tectonic setting: both accumulated in deep water adjacent to the steep, eroded margins of carbonate platforms — settings that subsequently sheltered the faunas from tectonic and metamorphic obliteration.
Antifungal activity of a Pinus monticola antimicrobial peptide 1 (Pm-AMP1) and its accumulation in western white pine infected with Cronartium ribicola
Authors: Zamany Arezoo , Liu Jun-Jun , Ekramoddoullah Abul , Sniezko Richard 
Published: August 2011

Pinus monticola antimicrobial peptide 1 (Pm-AMP1) was expressed and purified from bacterial cell lysate and its identity and purity confirmed by Western blot analysis using the Pm-AMP1 antibody. Application of Pm-AMP1 resulted in visible hyphal growth inhibition of Cronartium ribicola , Phellinus sulphurascens , Ophiostoma montium , and Ophiostoma clavigerum 3–12 days post-treatment. Pm-AMP1 also inhibited spore germination of several other phytopathogenic fungi by 32%–84% 5 days post-treatment. Microscopic examination of C. ribicola hyphae in contact with Pm-AMP1 showed distinct morphological changes. Seven western white pine ( Pinus monticola Douglas ex D. Don) families (Nos. 1, 2, 5, 6, 7, 8, 10) showing partial resistance to C. ribicola in the form of bark reaction (BR) were assessed by Western immunoblot for associations between Pm-AMP1 accumulation and family, phenotype, canker number, and virulence of C. ribicola. There was a significant difference (p < 0.001) in mean Pm-AMP1 protein accumulation between families, with higher levels detected in the full-sib BR families (Nos. 1, 2, 5) than the half-sib BR families (Nos. 6, 7). Family 8, previously described as a Mechanism ‘X’ BR family, had the highest number of BR seedlings and displayed high Pm-AMP1 levels, whereas the susceptible family (No. 10) showed the lowest levels (p < 0.05). Family 1 showed a significant association between Pm-AMP1 accumulation and overall seedling health (p < 0.01, R = 0.533), with higher protein levels observed in healthy versus severely infected seedlings. In general, low Pm-AMP1 levels were observed with an increase in the number of cankers per seedling (p < 0.05), and seedlings inoculated with the avirulent source of C. ribicola showed significantly higher Pm-AMP1 levels (p < 0.05) in the majority of BR families. Cis-acting regulatory elements, such as CCAAT binding factors, and an AG-motif binding protein were identified in the Pm-AMP1 promoter region. Multiple polymorphic sites were identified within the 5′ untranslated region and promoter regions. Our results suggest that Pm-AMP1 is involved in the western white pine defense response to fungal infection, as observed by its antifungal activity on C. ribicola and a range of phytopathogens as well as through its association with different indicators of resistance to C. ribicola.
Resuscitating Cancer Immunosurveillance: Selective Stimulation of DLL1-Notch Signaling in T cells Rescues T-cell Function and Inhibits Tumor Growth
Authors: Huang Yuhui , Lin Luping , Shanker Anil , Malhotra Anshu , Yang Li , Dikov Mikhail M. , Carbone David P. 
Published: August 2011

Abstract
Deficiencies in immune function that accumulate during cancer immunoediting lead to a progressive escape from host immunosurveillance. Therapies that correct or overcome these defects could have a powerful impact on cancer management, but current knowledge of the types and mechanisms of immune escape is still incomplete. Here, we report a novel mechanism of escape from T-cell immunity that is caused by reduction in levels of the Delta family Notch ligands DLL1 and DLL4 in hematopoietic microenvironments. An important mediator of this effect was an elevation in the levels of circulating VEGF. Selective activation of the DLL1-Notch signaling pathway in bone marrow precursors enhanced T-cell activation and inhibited tumor growth. Conversely, tumor growth led to inhibition of Delta family ligand signaling through Notch in the hematopoietic environment, resulting in suppressed T-cell function. Overall, our findings uncover a novel mechanism of tumoral immune escape and suggest that a soluble multivalent form of DLL1 may offer a generalized therapeutic intervention to stimulate T-cell immunity and suppress tumor growth. Cancer Res; 71(19); 6122–31. ©2011 AACR.
Genome-wide Methylation Analysis Identifies Genes Specific to Breast Cancer Hormone Receptor Status and Risk of Recurrence
Authors: Fackler Mary Jo , Umbricht Christopher B. , Williams Danielle , Argani Pedram , Cruz Leigh-Ann , Merino Vanessa F. , Teo Wei Wen , Zhang Zhe , Huang Peng , Visvananthan Kala , Marks Jeffrey , Ethier Stephen , Gray Joe W. , Wolff Antonio C. , Cope Leslie M. , Sukumar Saraswati 
Published: August 2011

Abstract
To better understand the biology of hormone receptor–positive and–negative breast cancer and to identify methylated gene markers of disease progression, we carried out a genome-wide methylation array analysis on 103 primary invasive breast cancers and 21 normal breast samples, using the Illumina Infinium HumanMethylation27 array that queried 27,578 CpG loci. Estrogen and/or progesterone receptor–positive tumors displayed more hypermethylated loci than estrogen receptor (ER)-negative tumors. However, the hypermethylated loci in ER-negative tumors were clustered closer to the transcriptional start site compared with ER-positive tumors. An ER-classifier set of CpG loci was identified, which independently partitioned primary tumors into ER subtypes. A total of 40 (32 novel and 8 previously known) CpG loci showed differential methylation specific to either ER-positive or ER-negative tumors. Each of the 40 ER subtype–specific loci was validated in silico, using an independent, publicly available methylome dataset from the Cancer Genome Atlas. In addition, we identified 100 methylated CpG loci that were significantly associated with disease progression; the majority of these loci were informative particularly in ER-negative breast cancer. Overall, the set was highly enriched in homeobox containing genes. This pilot study shows the robustness of the breast cancer methylome and illustrates its potential to stratify and reveal biological differences between ER subtypes of breast cancer. Furthermore, it defines candidate ER-specific markers and identifies potential markers predictive of outcome within ER subgroups. Cancer Res; 71(19); 6195–207. ©2011 AACR.
Upregulation of Rac GTPase-Activating Protein 1 Is Significantly Associated with the Early Recurrence of Human Hepatocellular Carcinoma
Authors: Wang Suk Mei , Ooi London Lucien P.J. , Hui Kam M. 
Published: August 2011

Abstract
Purpose: To assess the significance of Rac GTPase-activating protein 1 (RACGAP1) expression in identifying HBV-positive human hepatocellular carcinoma (HCC) patients who are at high risk for recurrent disease.
Experimental Design: The prognostic significance of RACGAP1 was compared with clinicopathologic parameters available at diagnosis using multivariate and log-rank test. RACGAP1 expression and outcome in recurrence was compared between 35 patients with recurrence and 41 patients without recurrence using Kaplan–Meier analysis. RACGAP1-targeted molecules and pathways were identified and characterized by inhibition with siRNA duplexes.
Results: Kaplan–Meier analysis showed that the level of RACGAP1 expression is sufficient to predict the early recurrence of HCC: high RACGAP1 expression correlates with high risk of postresection recurrent HCC (P &lt; 0.0005). Silencing of RACGAP1 in Hep3B and MHCC97-H HCC cells with high endogenous RACGAP1 expression inhibited cell migration and invasion. Using Ingenuity Pathway Analysis, the target molecules silenced in the RACGAP1 interactome were mostly genes related to the mitotic roles of the polo-like kinases. These included PRC1, AURKB, CDC2, ECT2, KIF23, PAK1, and PPP2R5E. In providing clinical corroboration of these results, when expression of these transcripts was analyzed in an expression database that we have established previously for HBV-positive HCC patients, these genes was mostly upregulated in patients who exhibited early recurrent disease and hence provided important corroboration of these results.
Conclusions: siRNA-silencing RACGAP1 mainly targeted genes in an interactome clinically relevant to early HCC recurrence. Besides being an independent informative prognostic biomarker, RACGAP1 could also be a potential molecular target for designing therapeutic strategies for HCC. Clin Cancer Res; 17(18); 6040–51. ©2011 AACR.
Preclinical Pharmacokinetics and Safety of Sym004: A Synergistic Antibody Mixture Directed against Epidermal Growth Factor Receptor
Authors: Skartved Niels Jørgen Østergaard , Jacobsen Helle Jane , Pedersen Mikkel Wandahl , Jensen Pernille Foged , Sen Jette Wagtberg , Jørgensen Thomas Kjærsgaard , Hey Adam , Kragh Michael 
Published: August 2011

Abstract
Purpose: Sym004 is a novel therapeutic antibody mixture product comprising two unmarketed monoclonal antibodies (mAb) targeting the epidermal growth factor receptor (EGFR). In previous preclinical proof-of-concept studies, Sym004 was shown to elicit superior cancer cell growth inhibition activities compared with marketed anti-EGFR mAbs. This article describes the design and results of the preclinical safety program conducted to support early clinical development of Sym004.
Experimental Design: Tissue cryosections from various species were stained with Sym004 to evaluate tissue cross reactivity. The pharmacokinetics of Sym004 were evaluated in a mouse xenograft model and in Cynomolgus monkeys. Monkeys received once weekly intravenous infusions of Sym004 in the range 2 to 24 mg/kg for 6 to 8 weeks. Cetuximab (a marketed anti-EGFR mAb) and the individual antibodies comprising Sym004 were included in the repeat-dose toxicity studies at single-dose level.
Results: Sym004 had a staining pattern similar to cetuximab in tissue panels from both human and non-human primates. Once weekly dosing of Sym004 to Cynomolgus monkeys did not cause accumulation, whereas administration of the individual antibodies resulted in prolonged half-life and accumulation. In direct comparisons with cetuximab, Sym004 did not induce any distinct or novel adverse findings in the animals. However, an early onset of pronounced, reversible, and anticipated anti-EGFR–mediated pharmacologic effects, such as skin rash, dehydration, and liquid feces, was observed. Only minor adverse effects were recorded in animals treated with the individual antibodies comprising Sym004.
Conclusion: Sym004 was well tolerated and did not induce any unexpected toxicities. The preclinical safety data enabled initiation of the ongoing clinical development. Clin Cancer Res; 17(18); 5962–72. ©2011 AACR.
The Heat Shock Protein 90 Inhibitor IPI-504 Induces KIT Degradation, Tumor Shrinkage, and Cell Proliferation Arrest in Xenograft Models of Gastrointestinal Stromal Tumors
Authors: Floris Giuseppe , Debiec-Rychter Maria , Wozniak Agnieszka , Stefan Cristiana , Normant Emmanuel , Faa Gavino , Machiels Kathleen , Vanleeuw Ulla , Sciot Raf , Schöffski Patrick 
Published: August 2011

Abstract
The activity of the receptor tyrosine kinase KIT is crucial for gastrointestinal stromal tumor (GIST) growth and survival. Imatinib and sunitinib are very effective in advanced GIST, but have no curative potential. The observation that heat shock protein 90 (HSP90) inhibition results in KIT degradation prompted us to assess the efficacy of the HSP90 inhibitor retaspimycin hydrochloride (IPI-504) alone or in combination with imatinib or sunitinib in two GIST xenografts with distinctive KIT mutations. Nude mice were grafted with human GIST carrying KIT exon 13 (GIST-882; n = 59) or exon 11 (GIST-PSW; n = 44) mutations and dosed with imatinib (50 mg/kg twice daily), sunitinib (40 mg/kg once daily), IPI-504 (100 mg/kg 3 times per week), IPI-504 + imatinib, or IPI-504 + sunitinib. We evaluated tumor volume, proliferation and apoptosis, KIT expression and activation, as well as adverse events during treatment. Treatment with IPI-504 alone resulted in tumor regression, proliferation arrest, and induction of tumor necrosis. We documented downregulation of KIT and its signaling cascade in IPI-504–treated animals. Treatment effects were enhanced by combining IPI-504 with imatinib or sunitinib. On histologic examination, liver damage was frequently observed in animals exposed to combination treatments. In conclusion, IPI-504 shows consistent antitumor activity and induces KIT downregulation in GIST, as a single agent, and is more potent in combination with imatinib or sunitinib. The sequence of drug administration in the combination arms warrants further studies. Mol Cancer Ther; 10(10); 1897–908. ©2011 AACR.
Antitumor Activity of Ridaforolimus and Potential Cell-Cycle Determinants of Sensitivity in Sarcoma and Endometrial Cancer Models
Authors: Squillace Rachel M. , Miller David , Cookson Michelle , Wardwell Scott D. , Moran Lauren , Clapham David , Wang Frank , Clackson Tim , Rivera Victor M. 
Published: August 2011

Abstract
Ridaforolimus is a nonprodrug rapamycin analogue that potently inhibits mTOR and has shown significant activity in patients with metastatic sarcoma and endometrial cancer, two diseases where high unmet need remains. Here, we evaluated the activity of ridaforolimus in preclinical models of these tumor types and used these models to explore molecular correlates of sensitivity. The in vitro sensitivity of a panel of sarcoma and endometrial cancer cell lines was established by measuring the effect of ridaforolimus on cell proliferation rate, revealing broad inhibition at low nanomolar concentrations. Additional benefit was found when ridaforolimus was combined with agents used to treat sarcoma and endometrial cancer patients. In vivo, potent antitumor activity of ridaforolimus associated with inhibition of mTOR signaling was observed in sarcoma and endometrial xenograft models. Immunoblot analysis was conducted to assess the expression and activation state of multiple signaling proteins in the phosphoinositide-3-kinase/AKT/mTOR and cell-cycle pathways. In endometrial but not sarcoma cell lines, the absence of PTEN or elevated levels of phosphorylated or total AKT was associated with greater sensitivity. However, in both tumor types, the proportion of cells in the G0–G1 phase before treatment correlated significantly with ridaforolimus sensitivity. Consistent with this, expression of several G1 phase cell-cycle proteins, notably p21 and p27, was higher in more sensitive lines. These results underscore the promise of ridaforolimus as a single agent or combination treatment of these tumor types and suggest novel potential predictive biomarkers of sensitivity to an mTOR inhibitor based on cell-cycle status. Mol Cancer Ther; 10(10); 1959–68. ©2011 AACR.
Inhibition of PARP-1 by Olaparib (AZD2281) Increases the Radiosensitivity of a Lung Tumor Xenograft
Authors: Senra Joana M. , Telfer Brian A. , Cherry Kim E. , McCrudden Cian M. , Hirst David G. , O'Connor Mark J. , Wedge Stephen R. , Stratford Ian J. 
Published: August 2011

AbstractPARP-1 is a critical enzyme in the repair of DNA strand breaks. Inhibition of PARP-1 increases the effectiveness of radiation in killing tumor cells. However, although the mechanism(s) are well understood for these radiosensitizing effects in vitro, the underlying mechanism(s) in vivo are less clear. Nicotinamide, a drug structurally related to the first generation PARP-1 inhibitor, 3-aminobenzamide, reduces tumor hypoxia by preventing transient cessations in tumor blood flow, thus improving tumor oxygenation and sensitivity to radiotherapy. Here, we investigate whether olaparib, a potent PARP-1 inhibitor, enhances radiotherapy, not only by inhibiting DNA repair but also by changing tumor vascular hemodynamics in non–small cell lung carcinoma (NSCLC). In irradiated Calu-6 and A549 cells, olaparib enhanced the cytotoxic effects of radiation (sensitizer enhancement ratio at 10% survival = 1.5 and 1.3) and DNA double-strand breaks persisted for at least 24 hours after treatment. Combination treatment of Calu-6 xenografts with olaparib and fractionated radiotherapy caused significant tumor regression (P = 0.007) relative to radiotherapy alone. To determine whether this radiosensitization was solely due to effects on DNA repair, we used a dorsal window chamber model to establish the drug/radiation effects on vessel dynamics. Olaparib alone, when given as single or multiple daily doses, or in combination with fractionated radiotherapy, increased the perfusion of tumor blood vessels. Furthermore, an ex vivo assay in phenylephrine preconstricted arteries confirmed olaparib to have higher vasodilatory properties than nicotinamide. This study suggests that olaparib warrants consideration for further development in combination with radiotherapy in clinical oncology settings such as NSCLC. Mol Cancer Ther; 10(10); 1949–58. ©2011 AACR.