bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of Seed Dispersal and Dispersal Failure in a Hawaiian Dry Forest Having Only Introduced Birds
Authors: Chimera Charles G. , Drake Donald R. 
Published: January 2010

ABSTRACTDry forests are among the most endangered natural communities in the Hawaiian Islands. Most have been reduced to isolated trees and small forest fragments in which native tree species reproduce poorly. The replacement of native birds by introduced generalists may be contributing to dry forest decline through modification of seed dispersal patterns. To document seed dispersal by introduced birds, we conducted foraging observations on fleshy‐fruited trees and measured seed rain under trees and in adjacent open areas for 1 year in a dry forest dominated by native trees. Although trees covered only 15.2 percent of the study area, 96.9 percent of the bird‐dispersed seeds were deposited beneath them. The Japanese white‐eye (Zosterops japonicus) was the principal dispersal agent. Among bird‐dispersed seeds, those of the invasive tree Bocconia frutescens accounted for 75 percent of all seeds collected beneath trees (14.8 seeds/m2/yr) and the invasive shrub Lantana camara accounted for 17 percent. Although nearly 60 percent of the reserve's native woody species possess fleshy fruits, introduced birds rarely disperse their seeds. Native trees accounted for <8 percent of all bird‐dispersed seeds and are consequently experiencing dispersal failure by falling directly under parent trees. Smaller‐seeded non‐native plants, in contrast, may be benefiting from dispersal by introduced birds. Current dispersal patterns suggest that these readily disseminated non‐native plants may eventually replace the remaining native flora.
Species‐Specific Growth Responses to Climate Variations in Understory Trees of a Central African Rain Forest
Authors: Couralet Camille , Sterck Frank J. , Sass‐Klaassen Ute , Van Acker Joris , Beeckman Hans 
Published: January 2010

ABSTRACTBasic knowledge of the relationships between tree growth and environmental variables is crucial for understanding forest dynamics and predicting vegetation responses to climate variations. Trees growing in tropical areas with a clear seasonality in rainfall often form annual growth rings. In the understory, however, tree growth is supposed to be mainly affected by interference for access to light and other resources. In the semi‐deciduous Mayombe forest of the Democratic Republic of Congo, the evergreen speciesAidia ochroleuca,Corynanthe paniculataandXylopia wilwerthiidominate the understory. We studied their wood to determine whether they form annual growth rings in response to changing climate conditions. Distinct growth rings were proved to be annual and triggered by a common external factor for the three species. Species‐specific site chronologies were thus constructed from the cross‐dated individual growth‐ring series. Correlation analysis with climatic variables revealed that annual radial stem growth is positively related to precipitation during the rainy season but at different months. The growth was found to associate with precipitation during the early rainy season forAidiabut at the end of the rainy season forCorynantheandXylopia. Our results suggest that a dendrochronological approach allows the understanding of climate–growth relationships in tropical forests, not only for canopy trees but also for evergreen understory species and thus arguably for the whole tree community. Global climate change influences climatic seasonality in tropical forest areas, which is likely to result in differential responses across species with a possible effect on forest composition over time.
Contrasting Population Dynamics of the Endemic New Caledonian ConiferAraucaria laubenfelsiiin Maquis and Rain Forest
Authors: Rigg Lesley S. , Enright Neal J. , Jaffré Tanguy , Perry George L. W. 
Published: January 2010

ABSTRACTThis study compares demographic parameters and population dynamics for high disturbance (maquis) and low disturbance (rain forest) environments of the montane conifer,Araucaria laubenfelsii, in New Caledonia. The establishment, growth, survival and reproduction ofca2500 individuals were followed in permanent plots over 10 yr. Growth and survival rates forA. laubenfelsiishow that it is a long‐lived, slow growing tree, with evidence of suppression in the sapling size classes in mature rain forest. Growth rates for all size classes are generally faster in maquis than rain forest. Transition matrix analyses estimated positive rates of population increase (λvalues>1), with populations expanding in maquis, and stable in mature forest.Araucaria laubenfelsiiis able to regenerate continuously in maquis and early successional rain forest, but recruitment is limited in older stands. Life table response experiment analyses showed that reproduction, and transitions from sapling to mature tree stage, contributed positively toλin maquis, but negatively in forest.Araucaria laubenfelsiion Mont Do can be considered a long‐lived pioneer, with early maquis colonizers helping to drive succession from maquis to forest. While opportunities for recruitment decline with time as rain forest sites develop a closed canopy, occasional gap phase recruitment, combined with disturbance by cyclones, landslides and fire, provide opportunities to ensure species persistence. Understanding contrasting population dynamics ofA. laubenfelsiiin maquis and rain forest will better facilitate conservation management of this species, particularly given current high rates of land conversion and degradation in New Caledonia.Abstract in French is available athttp://www.blackwell‐synergy.com/loi/btp
Macronutrient Regulation in the Tropical Terrestrial Ant Ectatomma ruidum (Formicidae): A Field Study in Costa Rica
Authors: Cook Steven C. , Behmer Spencer T. 
Published: January 2010

ABSTRACTUsing the geometric framework for the first time in a field study of ant nutritional biology, we show that Ectatomma ruidum colonies actively regulate protein–carbohydrate intake, self‐selecting a carbohydrate‐biased diet. These data, combined with quantitative recruitment data, provide a more comprehensive understanding of colony‐level nutritional requirements of ants.Abstract in Spanish is available at http://www.blackwell‐synergy.com/loi/btp
Higher Soluble Amyloid β Concentration in Frontal Cortex of Young Adults than in Normal Elderly or Alzheimer's Disease
Authors: Van Helmond Zoë , Miners J. Scott , Kehoe Patrick G. , Love Seth 
Published: January 2010

AbstractLittle is known about the relationship between soluble amyloid β (Aβ) and age. We have measured soluble and insoluble Aβ by enzyme‐linked immunosorbent assay (ELISA) in post‐mortem frontal cortex in normal brains (16–95 years) and AD. Insoluble Aβ increased with age, and was significantly higher in Alzheimer's disease (AD) than age‐matched controls. However, levels of soluble Aβ declined with age and were significantly greater in younger adults than older adults with or without AD. In AD, insoluble : soluble Aβ ratio was much higher than in age‐matched controls. The high levels of soluble Aβ in young adults included oligomeric species of Aβ1‐42. These observations do not preclude Aβ oligomers as neurotoxic mediators of AD but suggest that if they are, the toxicity may be restricted to certain species (eg, β‐pleated protofibrillar species not detected by our assay) or takes decades to manifest. The dramatically increased insoluble : soluble Aβ in AD points to an altered dynamic equilibrium of Aβ in AD, reflecting both enhanced aggregation and continued overproduction or impaired removal of the soluble peptide in older age, when the concentration of this peptide should be declining.
Glioma Pathophysiology: Insights Emerging from Proteomics
Authors: Deighton Ruth F. , McGregor Richard , Kemp Jocelyn , McCulloch James , Whittle Ian R. 
Published: January 2010

AbstractProteomics is increasingly employed in both neurological and oncological research to provide insight into the molecular basis of disease but rarely has a coherent, novel pathophysiological insight emerged. Gliomas account for >50% of adult primary intracranial tumors, with malignant gliomas (anaplastic astrocytomas and glioblastoma multiforme) being the most common. In glioma, the application of proteomic technology has identified altered protein expression but without consistency of these alterations or their biological significance being established. A systematic review of multiple independent proteomic analyses of glioma has demonstrated alterations of 99 different proteins. Importantly 10 of the 99 proteins found differentially expressed in glioma [PHB, Hsp20, serum albumin, epidermal growth factor receptor (EGFR), EA‐15, RhoGDI, APOA1, GFAP, HSP70, PDIA3] were identified in multiple publications. An assessment of protein–protein interactions between these proteins compiled using novel web‐based technology, revealed a robust and cohesive network for glioblastoma. The protein network discovered (containing TP53 and RB1 at its core) compliments recent findings in genomic studies of malignant glioma. The novel perspective provided by network analysis indicates that the potential of this technology to explore crucial aspects of glioma pathophysiology can now be realized but only if the conceptual and technical limitations highlighted in this review are addressed.
Chiral bis‐Acetal Porphyrazines as Near‐infrared Optical Agents for Detection and Treatment of Cancer
Authors: Trivedi Evan R. , Vesper Benjamin J. , Weitman Hana , Ehrenberg Benjamin , Barrett Anthony G.M. , Radosevich James A. , Hoffman Brian M. 
Published: January 2010

AbstractWe report the preparation of chiral oxygen atom‐appended porphyrazines (pzs) as biomedical optical agents that absorb and emit in the near‐IR wavelength range. These pzs take the form M[pz(A4‐nBn)], where “A” and “B” represent moieties appended to the pz’s pyrrole entities, A = (2R,3R) 2,3‐dimethyl‐2,3‐dimethoxy‐1,4‐diox‐2‐ene, B = β,β′‐di‐isopropoxybenzo, M is the incorporated metal ion (M = H2, Zn), and n = 0, 1, 2 (‐cis/‐trans) and 3 (Scheme 1). When dissolved in polar media, H2[pz(trans‐A2B2)] 5a does not fluoresce and has a negligible quantum yield for singlet oxygen generation (ФΔ = 0.074 ± 0.001, methanol), as measured by the photo‐oxidation of DMA. However, when sequestered in the nonpolar environment of a liposome, it displays strong NIR emission (λmax = 705 nm, Фf = 0.087) and an extremely high singlet oxygen quantum yield (ФΔ→1). Of this series, H2[pz(trans‐A2B2)] 5a is attractive as a potential optical probe, showing strongly fluorescent uptake by cells in culture, while 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide measurements of cell viability show no evidence of dark toxicity. This agent does show significant photoinduced toxicity suggesting that pzs such as 5a have promise as “theranostic” optical agents that can be visualized with fluorescence imaging while acting as a sensitizer for photodynamic therapy. Synthesis of Porphyrazines 3a–7a, 3b–7b.image
Identification of the Receptor Tyrosine Kinase c-Met and Its Ligand, Hepatocyte Growth Factor, as Therapeutic Targets in Clear Cell Sarcoma
Authors: Davis Ian J. , McFadden Andrew W. , Zhang Yixiang , Coxon Angela , Burgess Teresa L. , Wagner Andrew J. , Fisher David E. 
Published: January 2010

Abstract
Clear cell sarcoma (CCS), a childhood tumor of the tendons and aponeuroses, is uniformly fatal once it has metastasized because of its profound therapeutic resistance. CCS is characterized by production of a chimeric transcription factor, EWS-ATF1, which is formed as the result of a disease-specific chromosomal translocation. EWS-ATF1 activates the melanocyte transcription factor MITF, which in turn activates transcription of c-Met, an oncogenic receptor tyrosine kinase recently shown to be activated in CCS. Based on this connection, we hypothesized that c-Met inhibition may offer a strategy to treat CCS, as an indirect tactic to defeat a transforming pathway downstream of EWS-ATF1. Here, we show that primary CCS and CCS-derived cell lines express c-Met, which is activated in an autocrine fashion by its ligand hepatocyte growth factor (HGF)/scatter factor in some CCS cell lines. c-Met expression is critical for CCS invasion, chemotaxis, and survival. Blocking c-Met activity with a small-molecule inhibitor (SU11274) or a neutralizing antibody to its ligand HGF (AMG 102) significantly reduced CCS cell growth in culture. Similarly, AMG 102 significantly suppressed in vivo tumor growth in an autocrine xenograft model of CCS. Collectively, these findings suggest the HGF:c-Met signaling axis as a candidate therapeutic target to improve clinical management of CCS. Cancer Res; 70(2); 639–45
The High Mobility Group A1 Gene: Transforming Inflammatory Signals into Cancer?
Authors: Resar Linda M.S. 
Published: January 2010

Abstract
High mobility group A1 (HMGA1) is highly expressed during embryogenesis and in poorly differentiated cancers, and high levels portend a poor prognosis in some tumors. HMGA1 induces oncogenic transformation in cultured cells and causes aggressive cancers in transgenic mice, whereas blocking it interferes with transformation in experimental models. These findings suggest a pivotal role for HMGA1 in cancer. This review focuses on two recently described HMGA1 transcriptional targets that mediate inflammatory signals and drive malignant transformation because they could serve as biomarkers or therapeutic targets. Further elucidation of HMGA1 function in transformation promises to have a major impact on our war on cancer. Cancer Res; 70(2); 436–9
Sym004: A Novel Synergistic Anti–Epidermal Growth Factor Receptor Antibody Mixture with Superior Anticancer Efficacy
Authors: Pedersen Mikkel Wandahl , Jacobsen Helle Jane , Koefoed Klaus , Hey Adam , Pyke Charles , Haurum John Sørensen , Kragh Michael 
Published: January 2010

Abstract
Epidermal growth factor receptor (EGFR) is a validated therapeutic target in cancer and EGFR antagonists with greater effectiveness than existing clinical agents remain of interest. Here, we report a novel approach based on Sym004, a mixture of two anti-EGFR monoclonal antibodies directed against distinct nonoverlapping epitopes in EGFR extracellular domain III. Like anti-EGFR monoclonal antibodies in current clinical use, Sym004 inhibits cancer cell growth and survival by blocking ligand-binding receptor activation and phosphorylation and downstream receptor signaling. However, unlike the other antibodies, Sym004 induces rapid and efficient removal of the receptor from the cancer cell surface by triggering EGFR internalization and degradation. Compared with reference anti-EGFR monoclonal antibodies, Sym004 exhibited more pronounced growth inhibition in vitro and superior efficacy in vivo. Together, these findings illustrate a strategy to target EGFR more effectively than existing clinical antibodies. Cancer Res; 70(2); 588–97
Transcriptional Autoregulation by BRCA1
Authors: De Siervi Adriana , De Luca Paola , Byun Jung S. , Di Li Jun , Fufa Temesgen , Haggerty Cynthia M. , Vazquez Elba , Moiola Cristian , Longo Dan L. , Gardner Kevin 
Published: January 2010

Abstract
The BRCA1 gene product plays numerous roles in regulating genome integrity. Its role in assembling supermolecular complexes in response to DNA damage has been extensively studied; however, much less is understood about its role as a transcriptional coregulator. Loss or mutation is associated with hereditary breast and ovarian cancers, whereas altered expression occurs frequently in sporadic forms of breast cancer, suggesting that the control of BRCA1 transcription might be important to tumorigenesis. Here, we provide evidence of a striking linkage between the roles for BRCA1 as a transcriptional coregulator with control of its expression via an autoregulatory transcriptional loop. BRCA1 assembles with complexes containing E2F-1 and RB to form a repressive multicomponent transcriptional complex that inhibits BRCA1 promoter transcription. This complex is disrupted by genotoxic stress, resulting in the displacement of BRCA1 protein from the BRCA1 promoter and subsequent upregulation of BRCA1 transcription. Cells depleted of BRCA1 respond by upregulating BRCA1 transcripts, whereas cells overexpressing BRCA1 respond by downregulating BRCA1 transcripts. Tandem chromatin immmunoprecipitation studies show that BRCA1 is regulated by a dynamic coregulatory complex containing BRCA1, E2F1, and Rb at the BRCA1 promoter that is disrupted by DNA-damaging agents to increase its transcription. These results define a novel transcriptional mechanism of autoregulated homeostasis of BRCA1 that selectively titrates its levels to maintain genome integrity in response to genotoxic insult. Cancer Res; 70(2); 532–42
Oncogenic B-RafV600E Induces Spindle Abnormalities, Supernumerary Centrosomes, and Aneuploidy in Human Melanocytic Cells
Authors: Cui Yongping , Borysova Meghan K. , Johnson Joseph O. , Guadagno Thomas M. 
Published: January 2010

Abstract
Activating B-Raf mutations arise in 60% to 70% of human melanomas and are thought to play a vital role in tumorigenesis, although how this occurs remains poorly understood. Wild-type B-Raf is critical for normal mitosis of human somatic cells, suggesting that mutational activation of B-Raf might compromise mitosis. We examined this hypothesis by introducing oncogenic mutant B-RafV600E into established human melanoma cells, assessing the effects on mitosis and their possible relationship to extracellular signal–regulated kinase (ERK) pathway activation. Exogenous expression of this activated B-Raf mutant led to a high incidence of aberrant spindles and supernumerary centrosomes. These mitotic abnormalities were suppressed by expression of a B-RafV600E mutant–specific shRNA or by the addition of the mitogen-activated protein/ERK kinase–specific inhibitor U0126. Mitotic abnormalities generated by B-RafV600E also caused missegregation of chromosomes leading to aneuploidy. Because activating B-Raf mutations are detected frequently in benign nevi, we extended our studies to primary human melanocytes. Remarkably, short-term expression of B-RafV600E was sufficient to induce aneuploidy in human melanocytes or in immortalized human mammary epithelial cells. Collectively, our studies identify a novel role for the B-Raf oncogene in driving aneuploidy in melanocytic cells. We propose that disruption of mitotic controls by oncogenic B-Raf has important implications for understanding melanoma tumor development. Cancer Res; 70(2); 675–84
Myxoma Virus Virotherapy for Glioma in Immunocompetent Animal Models: Optimizing Administration Routes and Synergy with Rapamycin
Authors: Lun XueQing , Alain Tommy , Zemp Franz J. , Zhou Hongyuan , Rahman Masmudur M. , Hamilton Mark G. , McFadden Grant , Bell John , Senger Donna L. , Forsyth Peter A. 
Published: January 2010

AbstractOncolytic myxoma virus (MYXV) is being developed as a novel virotherapeutic against human brain cancer and has promising activity against human brain tumor models in immunocompromised hosts. Because an intact immune system could reduce its efficacy, the purpose of this study was to evaluate the oncolytic potential of MYXV in immunocompetent racine glioma models. Here, we report that MYXV infects and kills all racine cell glioma lines and that its effects are enhanced by rapamycin. Intratumoral administration of MYXV with rapamycin improved viral replication in the tumor and significantly prolonged host survival. Similarly, coadministration via a method of convection-enhanced delivery (CED) enhanced viral replication and efficacy in vivo. Mechanisms by which rapamycin improved MYXV oncolysis included an inhibition of type I IFN production in vitro and a reduction of intratumoral infiltration of CD68+ microglia/macrophages and CD163+ macrophages in vivo. Our findings define a method to improve MYXV efficacy against gliomas by rapamycin coadministration, which acts to promote immune responses engaged by viral delivery. Cancer Res; 70(2); 598–608
Oncogenic BRAF Mutation with CDKN2A Inactivation Is Characteristic of a Subset of Pediatric Malignant Astrocytomas
Authors: Schiffman Joshua D. , Hodgson J. Graeme , VandenBerg Scott R. , Flaherty Patrick , Polley Mei-Yin C. , Yu Mamie , Fisher Paul G. , Rowitch David H. , Ford James M. , Berger Mitchel S. , Ji Hanlee , Gutmann David H. , James C. David 
Published: January 2010

Abstract
Malignant astrocytomas are a deadly solid tumor in children. Limited understanding of their underlying genetic basis has contributed to modest progress in developing more effective therapies. In an effort to identify such alterations, we performed a genome-wide search for DNA copy number aberrations (CNA) in a panel of 33 tumors encompassing grade 1 through grade 4 tumors. Genomic amplifications of 10-fold or greater were restricted to grade 3 and 4 astrocytomas and included the MDM4 (1q32), PDGFRA (4q12), MET (7q21), CMYC (8q24), PVT1 (8q24), WNT5B (12p13), and IGF1R (15q26) genes. Homozygous deletions of CDKN2A (9p21), PTEN (10q26), and TP53 (17p3.1) were evident among grade 2 to 4 tumors. BRAF gene rearrangements that were indicated in three tumors prompted the discovery of KIAA1549-BRAF fusion transcripts expressed in 10 of 10 grade 1 astrocytomas and in none of the grade 2 to 4 tumors. In contrast, an oncogenic missense BRAF mutation (BRAFV600E) was detected in 7 of 31 grade 2 to 4 tumors but in none of the grade 1 tumors. BRAFV600E mutation seems to define a subset of malignant astrocytomas in children, in which there is frequent concomitant homozygous deletion of CDKN2A (five of seven cases). Taken together, these findings highlight BRAF as a frequent mutation target in pediatric astrocytomas, with distinct types of BRAF alteration occurring in grade 1 versus grade 2 to 4 tumors. Cancer Res; 70(2); 512–9
Chemopreventive Agent 3,3′-Diindolylmethane Selectively Induces Proteasomal Degradation of Class I Histone Deacetylases
Authors: Li Yongming , Li Xia , Guo Bin 
Published: January 2010

Abstract
3,3′-Diindolylmethane (DIM) is an anticancer agent that induces cell cycle arrest and apoptosis through unknown mechanisms. Here, we report that DIM can selectively induce proteasome-mediated degradation of class I histone deacetylases (HDAC1, HDAC2, HDAC3, and HDAC8) without affecting the class II HDAC proteins. DIM induced downregulation of class I HDACs in human colon cancer cells in vitro and in vivo in tumor xenografts. HDAC depletion relieved HDAC-mediated transcriptional inhibition of the cyclin-dependent kinase inhibitors p21WAF1 and p27KIP2, significantly increasing their expression and triggering cell cycle arrest in the G2 phase of the cell cycle. Additionally, HDAC depletion was associated with an induction of DNA damage that triggered apoptosis. Our findings indicate that DIM acts to selectively target the degradation of class I HDACs. Cancer Res; 70(2); 646–54