bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Analysis of Erythrocyte Invasion in
Plasmodium falciparum
Isolates from Senegal
Authors: Jennings Cameron V. , Ahouidi Ambroise D. , Zilversmit Martine , Bei Amy K. , Rayner Julian , Sarr Ousmane , Ndir Omar , Wirth Dyann F. , Mboup Souleymane , Duraisingh Manoj T. 
Published: May 2007

ABSTRACT

The human malaria parasite,
Plasmodium falciparum
, utilizes multiple ligand-receptor interactions for the invasion of human erythrocytes. Members of the reticulocyte binding protein homolog (PfRh) family have been shown to be critical for directing parasites to alternative erythrocyte receptors that define invasion pathways. Recent studies have identified gene amplification, sequence polymorphism, and variant expression of PfRh paralogs as mechanisms underlying discrimination between pathways for invasion. In this study, we find considerable heterogeneity in the invasion profiles of clonal, uncultured
P. falciparum
parasite isolates from a low-transmission area in Senegal. Molecular analyses revealed minimal variation in protein expression levels of the PfRh ligands, PfRh1, PfRh2a, and PfRh2b, and an absence of gene amplification in these isolates. However, significant sequence polymorphism was found within repeat regions of PfRh1, PfRh2a, and PfRh2b. Furthermore, we identified a large sequence deletion (∼0.58 kb) in the C-terminal region of the Pf
Rh2b
gene at a high prevalence in this population. In contrast to findings of earlier studies, we found no associations between specific sequence variants and distinct invasion pathways. Overall these data highlight the importance of region-specific elaborations in PfRh sequence and expression polymorphisms, which has important implications in our understanding of how the malaria parasite responds to polymorphisms in erythrocyte receptors and/or evades the immune system.
Characterization of Prostaglandin E2Production byCandida albicans
Authors: Erb-Downward John R. , Noverr Mairi C. 
Published: May 2007

ABSTRACTCandida albicansproduces lipid metabolites that are functionally similar to host prostaglandins. These studies, using mass spectrometry, demonstrate thatC. albicansproduces authentic prostaglandin E2(PGE2) from arachidonic acid. Maximal PGE2production was achieved at 37°C in stationary-phase culture supernatants and in cell-free lysates generated from stationary-phase cells. Interestingly, PGE2production is inhibited by both nonspecific cyclooxygenase and lipoxygenase inhibitors but not by inhibitors specific for the cyclooxygenase 2 isoenzyme. TheC. albicansgenome does not possess a cyclooxygenase homolog; however, several genes that may play a role in prostaglandin production fromC. albicanswere investigated. It was found that aC. albicansfatty acid desaturase homolog (Ole2) and a multicopper oxidase homolog (Fet3) play roles in prostaglandin production, withole2/ole2andfet3/fet3mutant strains exhibiting reduced PGE2levels compared with parent strains. This work demonstrates that the synthesis of PGE2inC. albicansproceeds via novel pathways.
Leishmania majorAbrogates Gamma Interferon-Induced Gene Expression in Human Macrophages from a Global Perspective
Authors: Dogra Nisha , Warburton Corinna , McMaster W. Robert 
Published: May 2007

ABSTRACTInfection withLeishmania majortriggers several pathways in the host cell that are crucial to initial infection as well as those that are used byLeishmaniato enhance its replication and virulence. To identify the molecular events of the host cell in response toLeishmania, the global gene expression of the human monocytic cell line THP-1 either infected withLeishmania majorin the presence and absence of gamma interferon (IFN-γ) or in the presence of IFN-γ alone was analyzed using high-density human oligonucleotide microarrays, followed by statistical analysis. The persistence of the parasite despite an extensive response to IFN-γ, added 24 h after infection withL. major, suggests thatL. majorcan survive in an IFN-γ-enriched environment in vitro. Results demonstrate thatL. majorcounteracts the IFN-γ response in macrophages on a large scale. Expression of genes involved in the innate immune response, cell adhesion, proteasomal degradation, Toll-like receptor expression, a variety of signaling molecules, and matrix metalloproteinases was significantly modulated.
Transcriptional Profiling of
Bacillus anthracis
during Infection of Host Macrophages
Authors: Bergman Nicholas H. , Anderson Erica C. , Swenson Ellen E. , Janes Brian K. , Fisher Nathan , Niemeyer Matthew M. , Miyoshi Amy D. , Hanna Philip C. 
Published: May 2007

ABSTRACT

The interaction between
Bacillus anthracis
and the mammalian phagocyte is one of the central stages in the progression of inhalational anthrax, and it is commonly believed that the host cell plays a key role in facilitating germination and dissemination of inhaled
B. anthracis
spores. Given this, a detailed definition of the survival strategies used by
B. anthracis
within the phagocyte is critical for our understanding of anthrax. In this study, we report the first genome-wide analysis of
B. anthracis
gene expression during infection of host phagocytes. We developed a technique for specific isolation of bacterial RNA from within infected murine macrophages, and we used custom
B. anthracis
microarrays to characterize the expression patterns occurring within intracellular bacteria throughout infection of the host phagocyte. We found that
B. anthracis
adapts very quickly to the intracellular environment, and our analyses identified metabolic pathways that appear to be important to the bacterium during intracellular growth, as well as individual genes that show significant induction in vivo. We used quantitative reverse transcription-PCR to verify that the expression trends that we observed by microarray analysis were valid, and we chose one gene (GBAA1941, encoding a putative transcriptional regulator) for further characterization. A deletion strain missing this gene showed no phenotype in vitro but was significantly attenuated in a mouse model of inhalational anthrax, suggesting that the microarray data described here provide not only the first comprehensive view of how
B. anthracis
survives within the host cell but also a number of promising leads for further research in anthrax.
Development of Fatal Colitis in FVB Mice Infected with
Citrobacter rodentium
Authors: Borenshtein Diana , Nambiar Prashant R. , Groff Elizabeth B. , Fox James G. , Schauer David B. 
Published: May 2007

ABSTRACT

Citrobacter rodentium
is the causative agent of transmissible murine colonic hyperplasia. The disease is characterized by severe but temporary epithelial hyperplasia with limited inflammation in the descending colon of adult mice on a variety of genetic backgrounds. The natural history of infection with this murine pathogen has been characterized in outbred Swiss Webster (SW) mice but not in the cognate inbred FVB strain. In contrast to subclinical infection in SW mice, 12-week-old FVB mice developed overt disease with significant weight loss and mortality beginning by 9 days postinoculation (dpi). By 21 dpi, more than 75% of infected FVB mice died or had to be euthanized, whereas no mortality developed in SW mice. Mortality in FVB mice was fully prevented by fluid therapy. Fecal shedding of bacteria was similar in both groups through 9 dpi; however, a slight but significant delay in bacterial clearance was observed in FVB mice by 12 to 18 dpi. SW mice developed hyperplasia with minimal inflammation in the descending colon. FVB mice developed epithelial cell hyperproliferation, severe inflammation with erosions and ulcers, and epithelial atypia by 6 dpi in the descending colon. In the majority of surviving FVB mice, colonic lesions, including epithelial atypia, were reversible, although a small percentage (5 to 7%) exhibited chronic colitis through 7 months postinoculation. The existence of susceptible and resistant lines of mice with similar genetic backgrounds will facilitate the identification of host factors responsible for the outcome of infection and may lead to the development of novel strategies for preventing and treating infectious colitis.
Artificial neural network forecasting of nonlinear Markov processes
Authors: Fleming Sean W 
Published: May 2007

I assessed the performance characteristics of the feed-forward artificial neural network (ANN) as a first-order nonlinear Markov modelling technique. The ability to recover the underlying structure of five synthetic random time series was first tested. The method was then applied to an observed geophysical time series, and the results were compared against external empirical constraints and a simple representation of the underlying physics. The Monte Carlo experiments suggested that the ANN–Markov technique: (i) yields good prediction skill; (ii) in general, accurately retrieves the form of the iterative mapping, even for extremely noisy data; (iii) accomplishes the foregoing without any need to consider or adjust for the distributional characteristics of the data or driving noise; and (iv) accurately estimates the distribution of the strictly stochastic signal component. Application to a historical river-flow record again showed good forecast skill. Moreover, the robustness, flexibility, and simplicity of the method permitted easy identification of the fundamental nonlinear physical dynamics of this environmental system directly from the time series data, perhaps belying the common perception of ANNs as a strictly black-box prediction technique. The ANN–Markov technique may thus serve as a valuable data-driven tool for guiding the development of both process-based and parameteric statistical models. The lack of specific distributional assumptions and requirements notwithstanding, it was also found that manual distributional transformations may permit the method to be tuned to particular applications by emphasizing or de-emphasizing certain features of the data. Drawbacks to the method include substantial data-set length requirements, a general limitation of ANNs, as well as an inconsistent but potentially troubling tendency to partially imprint the form of the ANN activation function upon the estimated recursion relationship. PACS Nos.: 02.50.Ga, 05.10.–a, 05.45.Tp, 07.05.Mh, 02.50.Ey, 92.40.Fb
Modern topics in theoretical nuclear physics
Authors: Jennings B K , Schwenk A 
Published: May 2007

Over the past five years there have been profound advances in nuclear physics based on effective field theory and the renormalization group. In this review, we summarize these advances and discuss how they impact our understanding of nuclear systems and experiments that seek to unravel their unknowns. We discuss future opportunities and focus on modern topics in low-energy nuclear physics, with special attention on the strong connections to many-body atomic and condensed-matter physics, as well as to astrophysics. This makes it an exciting era for nuclear physics. PACS Nos.: 21.60.–n, 21.30.Fe
Motion of a particle with extrinsic curvature in an electromagnetic field
Authors: Gryb S B , McKeon D GC 
Published: May 2007

The equations of motion for a particle whose free Lagrangian involves not only the arc length of its trajectory, but also its extrinsic curvature, is known to imply that the particle follows a helical path. We examine the parameters associated with this path to see if it can provide a realistic classical model for an electron. The radiation emitted by this point particle while following its helical trajectory is considered, and found to be well below the rest energy of the electron when the helical velocity of the electron is chosen to be 10–4c. PACS No.: 11:15Kc
The Folate Receptor α Is Frequently Overexpressed in Osteosarcoma Samples and Plays a Role in the Uptake of the Physiologic Substrate 5-Methyltetrahydrofolate
Authors: Yang Rui , Kolb E. Anders , Qin Jing , Chou Alexander , Sowers Rebecca , Hoang Bang , Healey John H. , Huvos Andrew G. , Meyers Paul A. , Gorlick Richard 
Published: May 2007

Abstract
Purpose: Two major systems exist for folate cell entry: the reduced folate carrier (RFC) and the folate receptor (FR). Although defective RFC-mediated transport was frequently identified as a mechanism of methotrexate (MTX) resistance in osteosarcoma, the status of FR and its role in this disease are unknown.
Experimental Design: mRNA for FRα was measured in 107 osteosarcoma specimens using quantitative reverse transcription-PCR and was related to RFC expression. The effect of FRα overexpression on MTX resistance and natural folate uptake was studied using FRα non-expressing osteosarcoma 143B cells transfected with FRα cDNA in comparison with those transfected with sense or antisense RFC in the same genetic background.
Results: Eighty-four samples (78.5%) had detectable FRα mRNA, and 29.9% had higher levels than the ovarian cancer cell line SKOV-3. No correlation was found between mRNA levels of FRα and RFC (r2 = 0.002). FRα overexpression had minor effects on the transport of MTX and sensitivity to this drug. Among the transfected 143B sublines, only the 143B-FRα was able to uptake 5-methyltetrahydrofolate when the extracellular concentration was reduced to 2 nmol/L, which conferred a growth advantage in physiologic folate concentrations compared with vector-only–transfected cells. Importantly, this was not similarly achieved by RFC overexpression.
Conclusions: This study suggests that FRα plays a role in the uptake of 5-methyltetrahydrofolate when the concentration gradient is insufficient for RFC-mediated transport. FRα overexpression is unlikely secondary to the decreased RFC expression in osteosarcoma.
Phase I and Pharmacokinetic Study of 7-Hydroxystaurosporine and Carboplatin in Advanced Solid Tumors
Authors: Edelman Martin J. , Bauer Kenneth S. , Wu Suhlan , Smith Ruth , Bisacia Sonia , Dancey Janet 
Published: May 2007

AbstractPurpose: Based on preclinical data showing synergy between 7-hydroxystaurosporine (UCN-01) and platinum agents, a phase I trial of carboplatin with UCN-01 administered as a 3 h infusion in patients with advanced solid tumors was done. The primary goals of this trial were to evaluate the tolerability of this combination and the pharmacokinetics of UCN-01 when administered over 3 h and to compare the tolerability and pharmacokinetics with previously described schedules.Patients and Methods: Patients with advanced solid tumors, good performance status, normal organ function, and no potentially curative therapy were eligible for the trial. Carboplatin was escalated from an area under the curve (AUC) of 3 to an AUC of 5. UCN-01 was escalated from 50 to 90 mg/m2.Results: Twenty-three patients with advanced solid tumors (20 with prior platinum treatment) received a total of 60 cycles of therapy. Full doses of both agents (carboplatin AUC 5, UCN-01 90 mg/m2 in cycle 1, 45 mg/m2 in subsequent cycles) could be administered. The major toxicity noted was hypotension, which could be abrogated with the use of saline prehydration and posthydration. No responses were seen; however, seven patients were able to receive more than two courses of therapy. Of note, two of three patients with refractory, progressive small cell lung cancer were able to receive six cycles of therapy without evidence of progression. One patient experienced resolution of paraneoplastic syndrome of inappropriate antidiuretic hormone. The pharmacokinetic variables Cmax and t1/2 of the 3 h infusion were essentially identical to those previously observed when UCN-01 was administered over 72 h. The average t1/2 for cycle 1 was 506 ± 301 h, and the mean Cmax for all dose levels was &gt;30 μmol/L. The mean AUC over the dosing interval for each dose level ranged from ∼6,000 to 9,000 μmol/L h. Thus, the AUC of UCN-01 after the 3 h infusion was lower than was observed after a 72 h infusion.Conclusion: The regimen of carboplatin and UCN-01 (administered as a 3 h infusion) was well tolerated. Further development of this combination, particularly in small cell lung cancer, is warranted.
Expression of a Peroxisome Proliferator-Activated Receptor γ1 Splice Variant that Was Identified in Human Lung Cancers Suppresses Cell Death Induced by Cisplatin and Oxidative Stress
Authors: Kim Hyo Jung , Hwang Jin-Yong , Kim Hyun Jun , Choi Wan Sung , Lee Jae Heun , Kim Hye Jung , Chang Ki Churl , Nishinaka Toru , Yabe-Nishimura Chihiro , Seo Han Geuk 
Published: May 2007

Abstract
Purpose: The activation of peroxisome proliferator-activated receptor γ (PPARγ) has been implicated in the inhibition of tumor progression in lung cancers through the induction of differentiation and apoptosis. Recently, we identified a novel splice variant of human PPARγ1 (hPPARγ1) that exhibits dominant-negative activity in human tumor-derived cell lines. This study aimed to examine the expression and pathophysiologic roles of a truncated splice variant of hPPARγ1 (hPPARγ1tr) in primary human lung cancer tissues.
Experimental Design: The expression and localization of hPPARγ1tr was surveyed in human primary lung cancer tissues using immunohistochemistry and Western blot analysis. Using transfectants stably expressing wild-type hPPARγ1 (hPPARγ1wt) and hPPARγ1tr, we also analyzed the pathophysiologic roles of hPPARγ1tr.
Results: We showed that PPARγ is expressed predominantly in the nucleus of nontumorous tissues, whereas it is present in both the nucleus and the cytoplasm of tumorous tissues in squamous cell carcinoma (SCC) of the lung. Western blot analysis confirmed the presence of PPARγ1tr in primary lung SCC tissue but not in nontumorous tissue. Expression of PPARγ1tr in Chinese hamster ovary cells attenuated their susceptibility to cell death induced by oxidative stress or cisplatin, whereas their susceptibility was completely recovered by down-regulation of PPARγ1tr with small interfering RNA.
Conclusions: hPPARγ1tr is expressed strongly in tumorous tissues of primary human lung SCC and its overexpression renders transfected cells more resistant to chemotherapeutic drug- and chemical-induced cell death. These data suggest that the decreased drug sensitivity of PPARγ1tr-expressing cells may be associated with increased tumor aggressiveness and poor clinical prognosis of patients.
Methylation of O6-Methylguanine DNA Methyltransferase and Loss of Heterozygosity on 19q and/or 17p Are Overlapping Features of Secondary Glioblastomas with Prolonged Survival
Authors: Eoli Marica , Menghi Francesca , Bruzzone Maria Grazia , De Simone Tiziana , Valletta Lorella , Pollo Bianca , Bissola Lorena , Silvani Antonio , Bianchessi Donatella , D'Incerti Ludovico , Filippini Graziella , Broggi Giovanni , Boiardi Amerigo , Finocchiaro Gaetano 
Published: May 2007

Abstract
Purpose: Recent data suggest that methylation of the DNA repair gene O6-methylguanine DNA methyltransferase (MGMT), by increasing the chemosensitivity of glioblastoma multiforme, is significantly associated with improved prognosis. Results in contradiction with these findings, however, are present in the literature and the clinical and genetic context framing MGMT methylation is poorly characterized.
Experimental Design: To address these issues, we have investigated the MGMT methylation status, clinical and magnetic resonance imaging characteristics, and relevant genetic features (loss of heterozygosity on 17p and 19q, EGFR amplification, and p53 mutations) in a retrospective study on 86 patients affected by glioblastoma multiforme: 72 patients had a clinical history indicating de novo insurgence of the tumor and the remaining 14 were secondary glioblastoma multiforme.
Results: MGMT methylation was detected by methylation-specific PCR in 41 of 86 cases (47.7%; Meth+). Progression-free survival and overall survival were significantly longer in Meth+ than in Meth− patients [10 versus 7 months (P = 0.003, log-rank test) and 18 versus 14 months (P = 0.0003, log-rank test), respectively]. Mixed-nodular enhancement at magnetic resonance imaging was significantly more frequent in Meth+ and secondary glioblastoma multiforme and ring enhancement in Meth− and primary glioblastoma multiforme (P &lt; 0.005). MGMT methylation was more present in secondary glioblastoma multiforme (P = 0.006) and associated with loss of heterozygosity on 17p and/or 19q (P = 0.005).
Conclusions: These observations suggest that MGMT methylation is part of a genetic signature of glioblastomas that developed from lower-grade gliomas.
Epigenetic Modifications of RASSF1A Gene through Chromatin Remodeling in Prostate Cancer
Authors: Kawamoto Ken , Okino Steven T. , Place Robert F. , Urakami Shinji , Hirata Hiroshi , Kikuno Nobuyuki , Kawakami Toshifumi , Tanaka Yuichiro , Pookot Deepa , Chen Zhong , Majid Shahana , Enokida Hideki , Nakagawa Masayuki , Dahiya Rajvir 
Published: May 2007

Abstract
Purpose: The RAS-association domain family 1, isoform A (RASSF1A) gene is shown to be inactivated in prostate cancers. However, the molecular mechanism of silencing of the RASSFIA gene is not fully understood. The present study was designed to investigate the mechanisms of inactivation of the RASSF1A gene through the analysis of CpG methylation and histone acetylation and H3 methylation associated with the RASSF1A promoter region.
Experimental Design: Methylation status of the RASSF1A gene was analyzed in 131 samples of prostate cancer, 65 samples of benign prostate hypertrophy (BPH), and human prostate cell lines using methylation-specific PCR. Histone acetylation (acetyl-H3, acetyl-H4) and H3 methylation (dimethyl-H3-K4, dimethyl-H3-K9) status associated with the promoter region in prostate cells were analyzed by chromatin immunoprecipitation (ChIP) assay.
Results: Aberrant methylation was detected in 97 (74.0%) prostate cancer samples and 12 (18.5%) BPH samples. The methylation frequency of RASSF1A showed a significant increase with high Gleason sum and high stage. The ChIP assays showed enhancement of histone acetylation and dimethyl-H3-K4 methylation on the unmethylated RASSF1A promoter. TSA alone was unable to alter key components of the histone code. However, after 5-aza-2′-deoxy-cytidine treatment, there was a complete reversal of the histone components in the hypermethylated promoter. Levels of acetyl-H3, acetyl-H4, and dimethyl-H3-K4 became more enriched, whereas H3K9me2 levels were severely depleted.
Conclusions: This is the first report suggesting that reduced histone acetylation or H3K4me2 methylation and increased dimethyl-H3-K9 methylation play a critical role in the maintenance of promoter DNA methylation–associated RASSF1A gene silencing in prostate cancer.