bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptation, migration or extirpation: climate change outcomes for tree populations
Authors: Aitken Sally N. , Yeaman Sam , Holliday Jason A. , Wang Tongli , Curtis‐McLane Sierra 
Published: January 2008

AbstractSpecies distribution models predict a wholesale redistribution of trees in the next century, yet migratory responses necessary to spatially track climates far exceed maximum post‐glacial rates. The extent to which populations will adapt will depend upon phenotypic variation, strength of selection, fecundity, interspecific competition, and biotic interactions. Populations of temperate and boreal trees show moderate to strong clines in phenology and growth along temperature gradients, indicating substantial local adaptation. Traits involved in local adaptation appear to be the product of small effects of many genes, and the resulting genotypic redundancy combined with high fecundity may facilitate rapid local adaptation despite high gene flow. Gene flow with preadapted alleles from warmer climates may promote adaptation and migration at the leading edge, while populations at the rear will likely face extirpation. Widespread species with large populations and high fecundity are likely to persist and adapt, but will likely suffer adaptational lag for a few generations. As all tree species will be suffering lags, interspecific competition may weaken, facilitating persistence under suboptimal conditions. Species with small populations, fragmented ranges, low fecundity, or suffering declines due to introduced insects or diseases should be candidates for facilitated migration.
PilB and PilT Are ATPases Acting Antagonistically in Type IV Pilus Function inMyxococcus xanthus
Authors: Jakovljevic Vladimir , Leonardy Simone , Hoppert Michael , Søgaard-Andersen Lotte 
Published: January 2008

ABSTRACTType IV pili (T4P) are dynamic surface structures that undergo cycles of extension and retraction. T4P dynamics center on the PilB and PilT proteins, which are members of the secretion ATPase superfamily of proteins. Here, we show that PilB and PilT of the T4P system inMyxococcus xanthushave ATPase activity in vitro. Using a structure-guided approach, we systematically mutagenized PilB and PilT to resolve whether both ATP binding and hydrolysis are important for PilB and PilT function in vivo. PilB as well as PilT ATPase activity was abolished in vitro by replacement of conserved residues in the Walker A and Walker B boxes that are involved in ATP binding and hydrolysis, respectively. PilB proteins containing mutant Walker A or Walker B boxes were nonfunctional in vivo and unable to support T4P extension. PilT proteins containing mutant Walker A or Walker B boxes were also nonfunctional in vivo and unable to support T4P retraction. These data provide genetic evidence that both ATP binding and hydrolysis by PilB are essential for T4P extension and that both ATP binding and hydrolysis by PilT are essential for T4P retraction. Thus, PilB and PilT are ATPases that act at distinct steps in the T4P extension/retraction cycle in vivo.
Molecular and Physiological Role of the Trehalose-Hydrolyzing α-Glucosidase from
Thermus thermophilus
HB27
Authors: Alarico Susana , da Costa Milton S. , Empadinhas Nuno 
Published: January 2008

ABSTRACT

Trehalose supports the growth of
Thermus thermophilus
strain HB27, but the absence of obvious genes for the hydrolysis of this disaccharide in the genome led us to search for enzymes for such a purpose. We expressed a putative α-glucosidase gene (TTC0107), characterized the recombinant enzyme, and found that the preferred substrate was α,α-1,1-trehalose, a new feature among α-glucosidases. The enzyme could also hydrolyze the disaccharides kojibiose and sucrose (α-1,2 linkage), nigerose and turanose (α-1,3), leucrose (α-1,5), isomaltose and palatinose (α-1,6), and maltose (α-1,4) to a lesser extent. Trehalose was not, however, a substrate for the highly homologous α-glucosidase from
T. thermophilus
strain GK24. The reciprocal replacement of a peptide containing eight amino acids in the α-glucosidases from strains HB27 (LGEHNLPP) and GK24 (EPTAYHTL) reduced the ability of the former to hydrolyze trehalose and provided trehalose-hydrolytic activity to the latter, showing that LGEHNLPP is necessary for trehalose recognition. Furthermore, disruption of the α-glucosidase gene significantly affected the growth of
T. thermophilus
HB27 in minimal medium supplemented with trehalose, isomaltose, sucrose, or palatinose, to a lesser extent with maltose, but not with cellobiose (not a substrate for the α-glucosidase), indicating that the α-glucosidase is important for the assimilation of those four disaccharides but that it is also implicated in maltose catabolism.
CAN THE BIG 3 OVERTAKE TOYOTA? — A STUDY BASED ON THE THEORY OF CONSTRAINTS
Authors: WU SIMON , WANG SAMUEL , BLOS MAURICIO F. , WEE H. M. 
Published: January 2008

Purpose — The aim of this paper is to provide answers to two significant questions. The first question is "what is the comprehensive action for the Big 3 to overtake Toyota Company?" The second question is "Can TOC (Theory of Constraints) really deal with this kind of complicated problem effectively?" Design/methodology/approach — In order to address this question and come out with a reasonable answer, this study uses the Theory of Constraints to discover the root causes and countermeasures for the Big 3 to break through their paradigms. Findings — It is worthwhile to highlight that we have demonstrated that a sophisticated case in global competition of the motor market can provide solutions with only four TOC logic trees. Furthermore, it is interesting to note that the four TOC logic trees fit perfectly well with each of the four problem solving steps in two aspects: (1) It provides a shortcut through mirror imaging process and (2) It enhances the clarity of the thinking process. Research limitations/implications — However, there remains some issues open for further exploration: (1) How can we make sure that the appropriate core problem(s) or root cause(s) has been identified in CRT (Current Reality Tree) and it is indeed the most meaningful one? (2) How can we proceed from CRT to FRT (Future Reality Tree) & further from FRT to PT (Prerequisites Tree) more effectively? (3) How can we discover key obstacles from PT and how to develop action plans from TT (Transition Tree) smoothly? (4) How to refine and integrate these feasible solution sets coming out from TT into the optimal solution scheme to be adapted in the real world? Originality/value — This study demonstrates how TOC problem solving can help to solve the core problems and root causes of "can the Big 3 overtake Toyota?" It not only gives managerial insights for the Big 3 to break through their paradigms to fight back Toyota; but also identify how a complex problem beyond production field can be analyzed and dealt with effectively. Paper type–Case study paper.
In vivo and Microarray Analysis of Rexinoid-Responsive Anaplastic Thyroid Carcinoma
Authors: Klopper Joshua P. , Berenz Andrew , Hays William R. , Sharma Vibha , Pugazhenthi Umarani , Janssen Jennifer , Singh Meenakshi , Bissonnette Reid P. , Haugen Bryan R. 
Published: January 2008

Abstract
Purpose: Anaplastic thyroid carcinoma is rare, yet lethal despite aggressive therapy. Molecular targeting may be beneficial using the rexinoid LGD1069, a retinoid X receptor–selective agonist, as a novel treatment. In this report, we describe the efficacy of LGD1069 in anaplastic thyroid carcinoma in vitro and assess the in vivo treatment effects on a responsive cancer. Additionally, we explore potential mediators of the rexinoid effect on a responsive anaplastic thyroid cancer using comparative microarray analysis.
Experimental Design: Anaplastic thyroid cancer cell lines DRO, ARO, and FRO were treated with LGD1069 in vitro. Responsive DRO xenograft tumors were treated with control chow or chow containing a low dose (30 mg/kg/d) or a high dose (100 mg/kg/d) of LGD1069. Comparative microarray analysis of DRO cells treated with LGD1069 compared with volume-equivalent control was assessed after 24 h of treatment to evaluate early gene expression changes.
Results: DRO xenograft tumor growth was inhibited by LGD1069 treatment in a dose-dependent manner. Comparative microarray analysis showed that 80 genes had a significant increase in expression and 29 genes had a decrease in expression after 24 h of treatment with LGD1069. Expression of angiopoietin-like 4 (ANGPTL4) mRNA was increased 6.5-fold. A trend towards an increase in ANGPTL4 mRNA (not statistically significant) was seen in treated tumors in vivo and this correlated with decreased tumor vascularity and increased necrosis.
Conclusions: LGD1069 therapy decreases proliferation in an anaplastic thyroid cancer cell line that expresses retinoid X receptor-γ, and this effect is confirmed with decreased tumor size in vivo in a nude mouse model. ANGPTL4 is increased in DRO in response to LGD1069 and may be a potential mediator of the effects of rexinoid treatment.
Overexpression of Cellular Iron Import Proteins Is Associated with Malignant Progression of Esophageal Adenocarcinoma
Authors: Boult Jessica , Roberts Keith , Brookes Matthew J. , Hughes Sharon , Bury Jonathan P. , Cross Simon S. , Anderson Gregory J. , Spychal Robert , Iqbal Tariq , Tselepis Chris 
Published: January 2008

Abstract
Purpose: There is growing evidence that iron is important in esophageal adenocarcinoma, a cancer whose incidence is rising faster than any other in the Western world. However, how iron mediates carcinogenesis at the molecular level remains unclear. In this study, we investigated the expression of iron transport proteins involved in cellular iron import, export, and storage in the premalignant lesion Barrett's metaplasia and esophageal adenocarcinoma.
Experimental Design: Perls' staining was used to examine iron deposition in tissue. mRNA expression in samples of Barrett's metaplasia matched with esophageal adenocarcinoma and samples of Barrett's metaplasia without evidence of adenocarcinoma were examined by real-time PCR. Semiquantitative immunohistochemistry was used to examine cellular localization and protein levels. The effect of iron loading on cellular proliferation and iron transporter expression was determined in esophageal cell lines OE33 and SEG-1 using a bromodeoxyuridine assay and real-time PCR, respectively.
Results: In the progression of Barrett's metaplasia to adenocarcinoma, there was overexpression of divalent metal transporter 1 (DMT1), transferrin receptor 1, duodenal cytochrome b, ferroportin, and H-ferritin, and these changes were associated with increased iron deposition. Overexpression of DMT1 was further associated with metastatic adenocarcinoma. Iron loading OE33 and SEG-1 cells caused increased cellular proliferation, which was associated with increased H-ferritin and decreased transferrin receptor 1 and DMT1 expression.
Conclusions: Progression to adenocarcinoma is associated with increased expression of iron import proteins. These events culminate in increased intracellular iron and cellular proliferation. This may represent a novel mechanism of esophageal carcinogenesis.
Imatinib Mesylate Enhances Therapeutic Effects of Gemcitabine in Human Malignant Mesothelioma Xenografts
Authors: Bertino Pietro , Piccardi Federica , Porta Camillo , Favoni Roberto , Cilli Michele , Mutti Luciano , Gaudino Giovanni 
Published: January 2008

AbstractPurpose: Platelet-derived growth factor receptor β (PDGFRβ), frequently activated in malignant mesothelioma, is a promising cancer therapeutic target. Imatinib mesylate (STI571; Glivec) is a selective inhibitor of tyrosine kinases as bcr-abl, c-kit, c-fms, and PDGFRβ and enhances tumor drug uptake by reducing the interstitial fluid pressure. We previously showed that imatinib mesylate synergizes with gemcitabine and pemetrexed in PDGFRβ-positive mesothelioma cells. Here, we aimed at investigating these combined treatments in a novel mesothelioma model.Experimental Design: REN mesothelioma cells, infected with a lentiviral vector carrying the luciferase gene, were injected in the peritoneum of severe combined immunodeficient mice. This model allowed imaging of live animals treated with pemetrexed or gemcitabine chemotherapeutics, or with imatinib mesylate alone, as well as with a combination of gemcitabine and imatinib mesylate.Results: We show here that, consistent with our previous in vitro studies, gemcitabine inhibited tumor growth, whereas pemetrexed was ineffective, even at the highest dosage tested. Compared with monotreatment, the combination of gemcitabine with imatinib mesylate led to a further tumor growth inhibition and improved mice survival, by a decrease rate of tumor cell proliferation and an increase in number of apoptotic tumor cells.Conclusions: Imatinib mesylate enhances the therapeutic response to gemcitabine, in accordance with our previous in vitro data. These in vivo results validate imatinib mesylate and gemcitabine as a combination treatment of malignant mesothelioma, also in view of its known positive effects on tumor drug uptake. These evidences provide the rationale for the currently ongoing clinical trials.
Dose and Schedule Study of Panitumumab Monotherapy in Patients with Advanced Solid Malignancies
Authors: Weiner Louis M. , Belldegrun Arie S. , Crawford Jeffrey , Tolcher Anthony W. , Lockbaum Pamela , Arends Rosalin H. , Navale Lynn , Amado Rafael G. , Schwab Gisela , Figlin Robert A. 
Published: January 2008

Abstract
Purpose: This phase 1 study evaluated the safety, pharmacokinetics, and activity of panitumumab, a fully human, IgG2 monoclonal antibody that targets the epidermal growth factor receptor in patients with previously treated epidermal growth factor receptor–expressing advanced solid tumors.
Experimental Design: Sequential cohorts were enrolled to receive four i.v. infusions of panitumumab monotherapy at various doses and schedules. Safety was continuously monitored. Serum samples for pharmacokinetic, immunogenicity, and chemistry assessments were drawn at preset intervals. Tumor response was assessed at week 8.
Results: Ninety-six patients received panitumumab. Median (range) age was 61 years (32-79 years), and 72 (75%) patients were male. Tumor types were 41% colorectal cancer, 22% prostate, 16% renal, 15% non–small cell lung, 3% pancreatic, 3% esophageal/gastroesophageal, and 1% anal. The overall incidence of grade 3 or 4 adverse events was 32% and 7%, respectively. The incidence of skin-related toxicities was dose dependent. No maximum tolerated dose was reached. No human anti-panitumumab antibodies were detected. No investigator-determined panitumumab infusion-related reactions were reported. Serum panitumumab concentrations were similar in the 2.5 mg/kg weekly, 6.0 mg/kg every 2 weeks, and 9.0 mg/kg every 3 weeks dose cohorts. Five of 39 patients (13%) with colorectal cancer had a confirmed partial response, and 9 of 39 patients (23%) with colorectal cancer had stable disease.
Conclusions: Panitumumab was well tolerated with comparable exposure and safety profiles for the weekly, every 2 weeks, and every 3 weeks administration schedules. Rash and dry skin occurred more frequently in the dose cohorts receiving ≥2.5 mg/kg weekly dose. Panitumumab has single-agent antitumor activity, most notably in patients with advanced colorectal cancer.
Vascular Endothelial Growth Factor Genotypes, Haplotypes, Gender, and the Risk of Non–Small Cell Lung Cancer
Authors: Zhai Rihong , Liu Geoffrey , Zhou Wei , Su Li , Heist Rebecca Suk , Lynch Thomas J. , Wain John C. , Asomaning Kofi , Lin Xihong , Christiani David C. 
Published: January 2008

Abstract
Purpose: The vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving tumor growth and metastasis. Polymorphisms in the VEGF gene may regulate VEGF production. In this large case-control study, we investigated whether functional polymorphisms (−460C/T, +405C/G, +936C/T) in the VEGF gene are associated with the risk of non–small cell lung cancer (NSCLC).
Experimental Design:VEGF genotypes and haplotypes were determined in 1,900 Caucasian patients with NSCLC and 1,458 healthy controls. The results were analyzed using logistic regression models, adjusting for age, gender, smoking status, pack-years of smoking, and years since smoking cessation (for ex-smokers). The false-positive report probability was estimated for the observed odds ratios (OR).
Results: There were no overall associations between individual VEGF genotypes and the risk of NSCLC. Stratified analysis suggested that the combined +405CC+CG genotype was significantly associated with increased risk of lung adenocarcinoma in males (adjusted OR, 1.40; 95% confidence interval, 1.03-1.87). In haplotype analysis, haplotypes were globally associated with differences between cases and controls in males (P = 0.03). Specifically, the −460T/+405G/+936C haplotype was significantly (P = 0.02) associated with decreased risk of adenocarcinoma in males when compared with the most common CGC haplotype (adjusted OR, 0.76; 95% confidence interval, 0.50-0.98). None of the VEGF genotypes and haplotypes studied significantly influenced the susceptibility to NSCLC in females.
Conclusions: Polymorphisms of −460C/T, +405C/G, and +936C/T in the VEGF gene do not play a major role in NSCLC risk. However, we could not exclude a minor role for the +405CC+CG genotypes and the 460T/+405G/+936C haplotype in lung adenocarcinogenesis in male Caucasians.
Unique Cell Surface Expression of Receptor Tyrosine Kinase ROR1 in Human B-Cell Chronic Lymphocytic Leukemia
Authors: Baskar Sivasubramanian , Kwong Ka Yin , Hofer Thomas , Levy Jessica M. , Kennedy Michael G. , Lee Elinor , Staudt Louis M. , Wilson Wyndham H. , Wiestner Adrian , Rader Christoph 
Published: January 2008

Abstract
Purpose: Gene expression profiling identified receptor tyrosine kinase ROR1, an embryonic protein involved in organogenesis, as a signature gene in B-cell chronic lymphocytic leukemia (B-CLL). To assess the suitability of ROR1 as a cell surface antigen for targeted therapy of B-CLL, we carried out a comprehensive analysis of ROR1 protein expression.
Experimental Design: Peripheral blood mononuclear cells, sera, and other adult tissues from B-CLL patients and healthy donors were analyzed qualitatively and quantitatively for ROR1 protein expression by flow cytometry, cell surface biotinylation, Western blotting, and ELISA.
Results: ROR1 protein is selectively expressed on the surface of B-CLL cells, whereas normal B cells, other normal blood cells, and normal adult tissues do not express cell surface ROR1. Moreover, cell surface expression of ROR1 is uniform and constitutive, i.e., independent of anatomic niches, independent of biological and clinical heterogeneity of B-CLL, independent of B-cell activation, and found at similar levels in all B-CLL samples tested. The antibody binding capacity of B-CLL cell surface ROR1 was determined to be in the range of 103 to 104 molecules per cell. A portion of B-CLL cell surface ROR1 was actively internalized upon antibody binding. Soluble ROR1 protein was detectable in sera of &lt;25% of B-CLL patients and a similar fraction of healthy donors at concentrations below 200 ng/mL.
Conclusions: The restricted, uniform, and constitutive cell surface expression of ROR1 protein in B-CLL provides a strong incentive for the development of targeted therapeutics such as monoclonal antibodies.
Sprycel for Chronic Myeloid Leukemia and Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia Resistant to or Intolerant of Imatinib Mesylate
Authors: Brave Michael , Goodman Vicki , Kaminskas Edvardas , Farrell Ann , Timmer William , Pope Sarah , Harapanhalli Ravi , Saber Haleh , Morse David , Bullock Julie , Men Angela , Noory Carol , Ramchandani Roshni , Kenna Leslie , Booth Brian , Gobburu Joga , Jiang Xiaoping , Sridhara Rajeshwari , Justice Robert , Pazdur Richard 
Published: January 2008

Abstract
Purpose: On June 28, 2006, the U.S. Food and Drug Administration approved dasatinib (Sprycel; Bristol-Myers Squibb), a new small-molecule inhibitor of multiple tyrosine kinases, for the treatment of adults with chronic phase, accelerated phase, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy including imatinib. This summary reviews the database supporting this approval.
Experimental Design: Four single-arm multicenter studies supported the efficacy and safety of dasatinib. The primary efficacy end point in chronic phase CML was major cytogenetic response. The primary end point in accelerated phase, myeloid phase, and lymphoid blast phase CML, and Ph+ ALL was major hematologic response.
Results: The four studies combined enrolled 445 patients. In patients with chronic phase CML, the major cytogenetic response rate was 45% with a complete cytogenetic response rate of 33%. Major hematologic response rates in patients with accelerated phase CML, myeloid CML, lymphoid blast CML, and Ph+ ALL were 59%, 32%, 31%, and 42%, respectively. Median response durations in chronic phase, accelerated phase, and myeloid phase CML had not been reached. The median durations of major hematologic response were 3.7 months in lymphoid blast CML and 4.8 months in Ph+ ALL. Common toxicities with dasatinib included myelosuppression, bleeding, and fluid retention.
Conclusions: This report describes the Food and Drug Administration review supporting the approval of dasatinib for CML and Ph+ ALL based on the rates and durability of cytogenetic and hematologic responses.
Sperm dimorphism in the free-living marine nematode Terschellingia glabricutis (Nematoda: Monhysterida: Linhomoeidae)
Authors: Yushin Vladimir 
Published: January 2008

AbstractThe structure and development of the dimorphic spermatozoa of the free-living marine nematode Terschellingia glabricutis (Monhysterida, Linhomoeina, Linhomoeidae) were studied with transmission electron microscope (TEM). The linhomoeid pattern of spermatozoa includes absence of fibrous bodies (FB) in spermatocytes and their appearance in spermatids as spindle-shaped bodies never associating with membranous organelles (MO); presence of centrioles near the sperm nucleus; occurrence of filopodia in the spermatids and immature spermatozoa; unpolarised concentric structure of the mature spermatozoa; microtubule-like elements in spermatids and spermatozoa. The linhomoeins differ from their closest relatives, monhysterins (Xyalidae, Sphaerolaimidae), by total absence of MO at all the stages of spermatogenesis. This peculiarity is also found in the sperm development of some chromadorids, desmodorids and tylenchomorphs. In T. glabricutis the anterior testis produces large (20 μm) 'macrospermatozoa' of the linhomoeid pattern; the posterior testis produces much smaller (10 μm) 'microspermatozoa' of simplified structure. The female genital tubes also contain two types of amoeboid spermatozoa of different size and internal structure. Thus, T. glabricutis demonstrates a pattern of sperm dimorphism in which each testis of the diorchic male produces its own type of spermatozoa. Both types are found in the genital tube of fertilised females. Such sperm dimorphism is known from light microscope observations for several distantly related marine species although the biological significance of this dimorphism is obscure.