bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does domestication mimic speciation? 1. A population-genetic analysis ofHordeum spontaneumandHordeum vulgarebased on AFLP and evolutionary considerations
Authors: Wei Yu Ming , Baum Bernard Rene , Nevo Eviatar , Zheng You Liang 
Published: April 2006

To answer the question whether Hordeum spontaneum K. Koch. and Hordeum vulgare L. are conspecific taxonomic entities or not”, we carried out an investigation with amplified restriction fragment length polymorphism (AFLP™) using H. vulgare cultivars, H. spontaneum from the Fertile Crescent, and material from China, primarily Xizang (Tibet), containing landraces and accessions identified morphologically as Hordeum agriocrithon Åberg. and H. spontaneum. Population genetic analyses and discriminant analyses were based on three groupings, H. vulgare, H. spontaneum, and H. agriocrithon, determined from morphology. To independently find groups, cluster analyses were carried out followed by population-genetic analyses and discriminant analyses of the clusters. The results of population-genetic analyses of morphologically based groups were not very different from those of comparable analyses of groups inferred from clustering. Based on 795 AFLP bands scored on 506 individuals, genetic diversity was 30% higher within H. spontaneum than within H. agriocrithon or H. vulgare. The variation among the three entities was 27.3% (FCT= 0.27) and among populations within the three was 40.4% (FSC= 0.56) leaving 32.3% (FST= 0.68) within populations/accessions. Three entities were clearly defined by clustering and supported by discriminant analyses, and then nomenclaturally formulated, two as species and one as an interspecific hybrid. The first, H. spontaneum, comprises populations in the Near East, the second, H. vulgare, comprises the cultivars, and the third, H. ×agriocrithon, comprises all barley landraces and hybrids from China as well as hybrids from the Near East. We discuss evolutionary perspectives of speciation and conclude that barley cultivars form a species distinct from the wild progenitor, H. spontaneum. This analysis may highlight the dilemma regarding other cultivated plants and domesticated animals, a still unresolved evolutionary–taxonomic problem.
In vitro measurements of the competitive interactions between two saprobic basidiomycetes onTypha latifolia
Authors: Schulz Michael J. , Cahill, James F. , Currah Randolph S. 
Published: April 2006

Psathyrella typhae (Kalchbr.) Pearson & Dennis forms small basidiomata (mushrooms) and Sclerotium hydrophilum Saccardo in Rothert numerous minute sclerotia at the base of senescent shoots of Typha latifolia L. To assess how the two might compete in nature, isolates of these fungi were paired on autoclaved leaf segments of T. latifolia and incubated at 15 and 25 °C. The relative abundance of each species in the segments was determined by macerating the leaf tissues and then transferring fragments of macerate to microplates containing two types of media: one conclusively demonstrated the presence of P. typhae while the other demonstrated the presence of S. hydrophilum. Relative numbers of microplate wells showing positive reactions for each species on each medium indicated the proportion of the segment occupied following single and paired inoculations. These data demonstrated that competition was asymmetric, with P. typhae the stronger competitor at both temperatures, and uninhibited by the presence of S. hydrophilum. In contrast, S. hydrophilum was competitively excluded by P. typhae.
Assessment of recent environmental changes in New Brunswick (Canada) lakes based on paleolimnological shifts in diatom species assemblages
Authors: Harris M. Anne , Cumming Brian F. , Smol John P. 
Published: April 2006

New Brunswick lakes are subjected to multiple environmental stressors, such as atmospheric acid deposition and climate change. In the absence of long-term environmental data, the impacts of these stressors are not well understood. Long-term effects of environmental change on diatom species assemblages were assessed in the sediments of 16 New Brunswick lakes using paleolimnological approaches. A regional trend of increasing Cyclotella stelligera Cleve & Gunrow and decreasing Aulacoseira species complex was recorded in most lakes. Detailed paleolimnological analyses of Wolfe, Cundy, and West Long lakes revealed varying degrees of species change, with assemblage shifts beginning ca. 1900 CE (common era). These species trends are not consistent with acidification. However, linear regression of mean July temperature with time for two New Brunswick historical instrumental temperature records revealed statistically significant warming over the past century. The shift from heavily silicified tychoplanktonic Aulacoseira species to small planktonic diatom species, such as C. stelligera, is consistent with paleolimnological inferences of warming trends recorded in several other lake regions of the Northern Hemisphere. These assemblage shifts are likely due to recent climate change and may be mediated by reduced ice cover and (or) increased thermal stability (decreased lake mixing) during the open water period.
Convergence and stability of a three-step iterative algorithm for a general quasi-variational inequality problem
Authors: Kazmi KR , Bhat MI 
Published: April 2006

AbstractWe consider a general quasi-variational inequality problem involving nonlinear, nonconvex and nondifferentiable term in uniformly smooth Banach space. Using retraction mapping and fixed point method, we study the existence of solution of general quasi-variational inequality problem and discuss the convergence analysis and stability of a three-step iterative algorithm for general quasi-variational inequality problem. The theorems presented in this paper generalize, improve, and unify many previously known results in the literature.
Gastrin Enhances the Angiogenic Potential of Endothelial Cells via Modulation of Heparin-Binding Epidermal-Like Growth Factor
Authors: Clarke Philip A. , Dickson Jacqueline H. , Harris Joseph C. , Grabowska Anna , Watson Susan A. 
Published: April 2006

Abstract
This study examined whether gastrin modulates endothelial cell activity via heparin-binding epidermal growth factor–like growth factor (HB-EGF) expression. Human umbilical vascular endothelial cells (HUVEC) were assessed for tubule formation in the presence of amidated gastrin-17 (G17) and glycine-extended gastrin-17 (GlyG17) peptides. HB-EGF gene and protein expressions were measured by quantitative reverse transcription-PCR, immunocytochemistry, and Western blotting, and HB-EGF shedding by ELISA. Matrix metalloproteinases MMP-2, MMP-3, and MMP-9 were assessed by Western blotting. Chick chorioallantoic membrane studies measured the in vivo angiogenic potential of gastrin and microvessel density (MVD) was assessed in large intestinal premalignant lesions of hypergastrinaemic APCMin mice. MVD was also examined in human colorectal tumor and resection margin normals and correlated with serum-amidated gastrin levels (via RIA) and HB-EGF protein expression (via immunohistochemistry). HUVEC cells showed increased tubule and node formation in response to G17 (186%, P &lt; 0.0005) and GlyG17 (194%, P &lt; 0.0005). This was blockaded by the cholecystokinin-2 receptor (CCK-2R) antagonists JB95008 and JMV1155 and by antiserum to gastrin and HB-EGF. Gastrin peptides increased HB-EGF gene expression/protein secretion in HUVEC and microvessel-derived endothelial cells and the levels of MMP-2, MMP-3, and MMP-9. G17 promoted angiogenesis in a chorioallantoic membrane assay, and MVD was significantly elevated in premalignant large intestinal tissue from hypergastrinaemic APCMin mice. In terms of the clinical situation, MVD in the normal mucosa surrounding colorectal adenocarcinomas correlated with patient serum gastrin levels and HB-EGF expression. Gastrin peptides, acting through the CCK-2R, enhance endothelial cell activity in models of angiogenesis. This may be mediated through enhanced expression and shedding of HB-EGF, possibly resulting from increased activity of matrix metalloproteinases. This proangiogenic effect translates to the in vivo and human situations and may add to the tumorigenic properties attributable to gastrin peptides in malignancy. (Cancer Res 2006; 66(7): 3504-12)
Inactivation of von Hippel-Lindau Gene Induces Constitutive Phosphorylation of MET Protein in Clear Cell Renal Carcinoma
Authors: Nakaigawa Noboru , Yao Masahiro , Baba Masaya , Kato Shingo , Kishida Takeshi , Hattori Keiko , Nagashima Yoji , Kubota Yoshinobu 
Published: April 2006

Abstract
It is well known that inactivation of von Hippel-Lindau (VHL) gene predisposes for human clear cell renal carcinoma (CCRC). However, details about critical roles of VHL inactivation during tumorigenesis are still unknown. MET protein is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF), which regulates cell growth, cell morphology, and cell motility. We showed that MET protein overexpressed in CCRC cells was phosphorylated without HGF/SF. This constitutive phosphorylation of MET protein in CCRC cells was inhibited by the rescue of exogenous wild-type VHL gene without a decrease in expression level of MET protein. Interestingly, wild-type VHL gene suppressed the phosphorylation of MET protein only under high cell density conditions. Additionally, MET protein activated by the inactivation of VHL gene modified cell adherence, including N-cadherin and β-catenin. When activation of MET protein in CCRC cells was inhibited by the MET inhibitor K252a, the growth of CCRC cells in vitro and the tumorigenesis induced by CCRC cells in nude mice were suppressed. From these results, we concluded that inactivation of VHL gene induced constitutive phosphorylation of MET protein and modified intercellular adherence structure to trigger the cell growth released from contact inhibition, finally resulting in tumorigenesis. This is one of the mechanisms of CCRC oncogenesis, and MET protein has potential as a molecular target for novel CCRC therapies. (Cancer Res 2006; 66(7): 3699-705)
Targeted Ablation of Par-4 Reveals a Cell Type–Specific Susceptibility to Apoptosis-Inducing Agents
Authors: Affar El Bachir , Po-shan Luke Margaret , Gay Frédérique , Calvo Dominica , Sui Guangchao , Weiss Robert S. , Li En , Shi Yang 
Published: April 2006

Abstract
The prostate apoptosis response-4 (Par-4) protein has been shown to function as an effector of cell death in response to various apoptotic stimuli, and down-regulation of this protein has been suggested to be a key event during tumorigenesis. Several studies suggest an essential function for the COOH-terminal leucine repeats/death domain of Par-4 in mediating apoptosis. We investigated the biological role of this domain in vivo by generating knock-out mice expressing a Par-4 mutant protein lacking the COOH terminus domain. We found that the Par-4 mutant mice are viable and fertile with no overt phenotype, thus excluding an essential role for the COOH terminus domain of Par-4 in embryogenesis and developmental apoptosis. To determine the requirement of Par-4 for apoptosis, we treated primary fibroblasts with various stimuli that trigger mitochondria and membrane receptor cell death pathways. Fibroblasts isolated from Par-4 mutant mice are as sensitive as the wild-type cells to these apoptosis-inducing agents. Similar effects were observed following RNA interference (RNAi)–mediated knockdown of Par-4 in these cells. In contrast, RNAi-mediated depletion of Par-4 in HeLa cells resulted in a significant inhibition of apoptosis induced by various proapoptotic agents. Taken together, our findings provide strong genetic evidence that the proapoptotic function of Par-4 is dependent on the cellular context and raise the possibility that alterations of Par-4 function may occur during carcinogenesis. (Cancer Res 2006; 66(7): 3456-62)
Simultaneous Inhibition of PDK1/AKT and Fms-Like Tyrosine Kinase 3 Signaling by a Small-Molecule KP372-1 Induces Mitochondrial Dysfunction and Apoptosis in Acute Myelogenous Leukemia
Authors: Zeng Zhihong , Samudio Ismael J. , Zhang Weiguo , Estrov Zeev , Pelicano Hélène , Harris David , Frolova Olga , Hail Numsen , Chen Wenjing , Kornblau Steven M. , Huang Peng , Lu Yiling , Mills Gordon B. , Andreeff Michael , Konopleva Marina 
Published: April 2006

Abstract
Phosphoinositol-3-kinase (PI3K)/protein kinase B (AKT) and Fms-like tyrosine kinase 3 (FLT3) signaling are aberrantly activated in acute myelogenous leukemia (AML) cells. Constitutively activated AKT and FLT3 regulate leukemia cell survival and resistance to chemotherapy. In this study, we investigated the effects of the novel multiple kinase inhibitor KP372-1 on the survival of AML cell lines and primary AML samples. KP372-1 directly inhibited the kinase activity of AKT, PDK1, and FLT3 in a concentration-dependent manner. Western blot analysis indicated that KP372-1 decreased the phosphorylation of AKT on both Ser473 and Thr308; abrogated the phosphorylation of p70S6 kinase, BAD, and Foxo3a via PI3K/AKT signaling; and down-regulated expression of PIM-1 through direct inhibition of FLT3. Treatment of AML cell lines with KP372-1 resulted in rapid generation of reactive oxygen species and stimulation of oxygen consumption, followed by mitochondrial depolarization, caspase activation, and phosphatidylserine externalization. KP372-1 induced pronounced apoptosis in AML cell lines and primary samples irrespective of their FLT3 status, but not in normal CD34+ cells. Moreover, KP372-1 markedly decreased the colony-forming ability of primary AML samples (IC50 &lt; 200 nmol/L) with minimal cytotoxic effects on normal progenitor cells. Taken together, our results show that the simultaneous inhibition of critical prosurvival kinases by KP372-1 leads to mitochondrial dysfunction and apoptosis of AML but not normal hematopoietic progenitor cells. (Cancer Res 2006; 66(7): 3737-46)
Adenoviral Gene Transfer of Stromal Cell–Derived Factor-1 to Murine Tumors Induces the Accumulation of Dendritic Cells and Suppresses Tumor Growth
Authors: Fushimi Toshiaki , O'Connor Timothy P. , Crystal Ronald G. 
Published: April 2006

AbstractThe human CXC chemokine, stromal cell–derived factor 1 (SDF-1α), is known to function in vitro as a chemotactic factor for lymphocytes, monocytes, and dendritic cells. In the context that dendritic cells are powerful antigen-presenting cells, we hypothesized that adenoviral gene transfer of SDF-1α to tumors might inhibit growth of preexisting tumors through attracting dendritic cells to the tumor. AdSDF-1α mediated the expression of SDF-1α mRNA and protein in A549 cells in vitro, and the supernatant of the AdSDF-1α-infected A549 cells showed chemotactic activity for dendritic cells. When syngeneic murine CT26 colon carcinoma tumors (BALB/c) and B16 melanoma and Lewis lung cell carcinoma (C57Bl/6) were injected with AdSDF-1α (5 × 108 plaque-forming units), there was an accumulation of dendritic cells and CD8+ cells within the tumor and significant inhibition of tumor growth compared with tumors injected with PBS or AdNull (control vector). The injection of AdSDF-1α into tumors induced the inflammatory enlargement and the accumulation of dendritic cells in the draining lymph node. Intratumoral AdSDF-1α administration elicited tumor-specific CTLs and adoptive transfer of splenocytes from AdSDF-1α-treated mice resulted in the elongation of survival after tumor challenge. Interestingly, in wild-type and CD4−/− mice but not in CD8−/− mice, AdSDF-1α inhibited the growth of the tumor. These observations suggest that adenoviral gene transfer of SDF-1α may be a useful strategy to accumulate dendritic cells in tumors and evoke antitumor immune responses to inhibit tumor growth. (Cancer Res 2006; 66(7): 3513-22)
PGP9.5 Methylation in Diffuse-Type Gastric Cancer
Authors: Yamashita Keishi , Park Hannah Lui , Kim Myoung Sook , Osada Motonobu , Tokumaru Yutaka , Inoue Hiroshi , Mori Masaki , Sidransky David 
Published: April 2006

Abstract
Diffuse-type gastric cancer (DGC) is the most deadly form of gastric cancer and is frequently accompanied by peritoneal dissemination and metastasis. The specific molecular events involved in DGC pathogenesis remain elusive. Accumulating evidence of epigenetic inactivation in tumor suppressor genes led us to conduct a comprehensive screen to identify novel methylated genes in human cancers using pharmacologic unmasking and subsequent microarray analysis. We compared differential RNA expression profiles of DGC and intestinal-type gastric cancer (IGC) cell lines treated with 5-aza-2′-deoxycytidine using microarrays containing 22,284 genes. We identified 16 methylated genes, including many novel genes, in DGC cell lines and studied PGP9.5 with particular interest. In primary gastric cancers, PGP9.5 was found to be more frequently methylated in DGCs (78%) than in IGCs (36%; DGC versus IGC, P &lt; 0.05). Furthermore, real-time methylation-specific PCR analysis of PGP9.5 showed relatively higher methylation levels in DGC than in IGC. Our data thus implicate a molecular event common in the DGC phenotype compared with IGC. (Cancer Res 2006; 66(7): 3921-7)
3p21.3 Tumor Suppressor Gene H37/Luca15/RBM5 Inhibits Growth of Human Lung Cancer Cells through Cell Cycle Arrest and Apoptosis
Authors: Oh Juliana J. , Razfar Ali , Delgado Idolina , Reed Rebecca A. , Malkina Anna , Boctor Baher , Slamon Dennis J. 
Published: April 2006

Abstract
Deletion at chromosome 3p21.3 is the earliest and the most frequently observed genetic alteration in lung cancer, suggesting that the region contains tumor suppressor gene(s) (TSG). Identification of those genes may lead to the development both of biomarkers to identify high-risk individuals and novel therapeutics. Previously, we cloned the H37/Luca15/RBM5 gene from 3p21.3 and showed its TSG characteristics. To investigate the physiologic function of H37 in the lung and its mechanism of tumor suppression, we have stably transfected H37 into A549 non–small cell lung cancer cells. A549/H37 cells show significant growth inhibition compared with the vector controls by in vitro and in vivo cell proliferation assays. Using this lung cancer cell model, we have found that the molecular mechanism of H37 tumor suppression involves both cell cycle (G1) arrest and apoptosis. To further define H37's function in cell cycle/apoptotic pathways, we investigated differential expression profiles of various cell cycle and apoptosis regulatory proteins using Western blot analysis. Both cyclin A and phophorylated RB levels were decreased in H37-transfected cells, whereas expression of Bax protein was increased. Mitochondrial regulation of apoptosis further downstream of Bax was investigated, showing change in the mitochondrial membrane potential, cytochrome c release into the cytosol, and enhanced caspase-9 and caspase-3 activities. We also report that H37 may mediate apoptosis in a p53-independent manner, and Bax knockdown by small interfering RNA suggests Bax plays a functional role downstream of H37. Lastly, we proposed a tumor suppression model of H37 as a post-transcriptional regulator for cell cycle/apoptotic–related proteins. (Cancer Res 2006; (66)7: 3419-27)
Improvement of the Tumor-Suppressive Effect of Boron Neutron Capture Therapy for Amelanotic Melanoma by Intratumoral Injection of the Tyrosinase Gene
Authors: Morita Norimasa , Hiratsuka Junichi , Kondoh Hirohumi , Uno Masako , Asano Tomoyuki , Niki Yoko , Sakurai Yoshinori , Ono Koji , Harada Tamotsu , Imajo Yoshinari 
Published: April 2006

Abstract
Boron neutron capture therapy (BNCT) is successful when there is a sufficient 10B concentration in tumor cells. In melanoma, 10B-para-boronophenylalanine (BPA) accumulation is proportional to melanin-producing activity. This study was done to confirm enhancement of the tumor-suppressive effect of BNCT on amelanotic melanoma by intratumoral injection of the tyrosinase gene. D178 or FF amelanotic melanomas were implanted s.c. in Syrian hamsters. One group of D178- or FF-bearing hamsters (TD178 or TFF group) received intratumoral injections of pcDNA-Tyrs constructed as a tyrosinase expression plasmid. The other hamsters (pD178 and pFF groups) were injected with pUC119, and control hamsters (D178 and FF groups) only with transfection reagents. All the groups underwent immunofluorescence analysis of tyrosinase expression and BPA biodistribution studies. BNCT experiments were done at the Kyoto University Research Reactor. Tyrosinase expression increased in the tumors of the TD178 and TFF groups but remained the same in the pD178 and pFF groups. Tumor boron concentrations in the TD178 and TFF groups increased significantly (TD178: 49.7 ± 12.6 versus D178: 27.2 ± 4.9 μg/g, P &lt; 0.0001; TFF: 30.7 ± 6.6 versus FF: 13.0 ± 4.7 μg/g, P &lt; 0.0001). The BNCT tumor-suppressive effect was marked in the TD178 and TFF groups. In vivo transfection with the tyrosinase gene increased BPA accumulation in the tumors, the BNCT tumor-suppressive effect on amelanotic melanoma being significantly enhanced. These findings suggest a potential new clinical strategy for the treatment of amelanotic melanoma with BNCT. (Cancer Res 2006; 66(7): 3747-53)
Gonadotropins Activate Proteolysis and Increase Invasion through Protein Kinase A and Phosphatidylinositol 3-Kinase Pathways in Human Epithelial Ovarian Cancer Cells
Authors: Choi Jung-Hye , Choi Kyung-Chul , Auersperg Nelly , Leung Peter C.K. 
Published: April 2006

Abstract
Despite evidence that gonadotropins may facilitate peritoneal metastasis of ovarian cancer by increasing cell adhesion, the action and molecular mechanism of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in ovarian cancer invasion is not well characterized. In the present study, we investigated the effects of FSH and LH on the invasive activity and the expression of metastasis-related proteinases in human epithelial ovarian cancer by Western blot, zymography, reverse transcription-PCR (RT-PCR), ELISA, and Boyden chamber assay. Treatment with FSH or LH (10, 100, or 1,000 ng/mL) significantly increased the invasion of ovarian cancer cell lines, including BG-1, CaOV-3, and SKOV-3 cells but not OVCAR-3 cells. In addition, treatment of SKOV-3 cells with FSH or LH (100 or 1,000 ng/mL) enhanced the expression and activation of matrix metalloproteinases (MMP-2 and MMP-9) as shown by RT-PCR, gelatin zymography, and ELISA. Pretreatment with [(2R)-2-(hydroxamido-carbonylmethyl)-4-methylpentanoyl]-l-tryptophan methylamide (10 μmol/L), a total MMP inhibitor, and 3-(4-phenoxyphenylsulfonyl)-propylthiirane (20 μmol/L), a specific gelatinase inhibitor, neutralized the proinvasive effect of gonadotropins in SKOV-3 cells. In addition, the secretion of tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2) and plasminogen activator inhibitor-1 was significantly decreased by FSH and LH (100 or 1,000 ng/mL). We further showed that gonadotropins induced an increase in SKOV-3 invasiveness via the activation of protein kinase A (PKA) and phosphatidylinositol 3-kinase (PI3K) signaling pathways. Taken together, these results suggest that gonadotropins may contribute to ovarian cancer metastasis via activation of proteolysis and increase in invasion through the PKA and PI3K pathways. (Cancer Res 2006; 66(7): 3912-20)