bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon Isotope Fractionation of PCE and TCE During Dechlorination by Vitamin B12
Authors: Slater G.F. , Lollar B. Sherwood , Lesage S. , Brown S.
Published: February 2007

Reductive dechlorination of perchloroethylene (PCE) and trichloroethylene (TCE) by vitamin B12 is an analogue of the microbial reductive dechlorination reaction and is presently being applied as a remediation technique. Stable carbon isotopic analysis, an effective and powerful tool for the investigation and monitoring of contaminant remediation, was used to characterize the isotopic effects of reductive dechlorination of PCE and TCE by vitamin B12 in laboratory microcosms. In laboratory experiments, 10 mg/L vitamin B12 degraded >90% of the initial 20 mg/L PCE with TCE, the primary product of PCE degradation, accounting for between 64% and 72% of the PCE degraded. In experiments with TCE, 147 mg/L vitamin B12 degraded >90% of the initial 20 mg/L TCE with cis‐dichloroethene (cDCE), the primary product of degradation accounting for between 30% and 35% of the TCE degraded. Degradation of both PCE and TCE exhibited first‐order kinetics. Strong isotopic fractionation of the reactant PCE and of the reactant TCE was observed over the course of degradation. This fractionation could be described with a Rayleigh model using enrichment factors of −16.5%o and −15.8%o for PCE, and −17.2%o and −16.6%o for TCE. Fractionation was similar in all experiments, with a mean enrichment factor of −16.5%o ± 0.6%o. The occurrence of such large enrichment factors indicates that isotopic analysis can be used to monitor the dechlorination of PCE and TCE by vitamin B12 and remediation of ground water plumes. Evidence indicates that isotopic fractionation is taking place during complexation of the chlorinated ethenes to vitamin B12, as has been suggested for reductive dechlorination by zero valent iron. The differences between e values for this reaction and those observed for anaerobic biodegradation of the chlorinated ethenes suggest that there may be differences in the rate‐determining step for these two processes.
Natural Gradient Tracer Test to Evaluate Natural Attenuation of MTBE Under Anaerobic Conditions
Authors: Amerson Illa , Johnson Richard L.
Published: February 2007

A natural gradient tracer test using perdeuterated MTBE was conducted in an anaerobic aquifer to determine the relative importance of dispersion and degradation in reducing MTBE concentrations in ground water. Preliminary ground water chemistry and hydraulic conductivity data were used to place the tracer within an existing dissolved MTBE plume at Port Hueneme, California. Following one year of transport, the tracer plume was characterized in detail.

Longitudinal dispersion was identified as the dominant mechanism for lowering the perdeuterated MTBE concentrations. The method of moments was used to determine the longitudinal and lateral dispersion coefficients (0.85 m2/day and 0.08 m2/day, respectively). A mass‐balance analysis, carried out after one year of transport, accounted for 110% of the injected mass and indicated that no significant mass loss occurred. The plume structure created by zones of higher and lower hydraulic conductivity at the site was complex, consisting of several localized areas of high tracer concentration in a lower concentration plume. This is important because the aquifer has generally been characterized as exhibiting fairly minor heterogeneity. In addition, the tracer plume followed a curved flowpath that deviated from the more macroscopic direction of ground water flow inferred from local ground water elevation measurements and the behavior of the existing plume. Understanding the mass balance, plume structure, curvature of the tracer plume, and consequently natural attenuation behavior required the detailed sampling approach employed in this study. These data imply that a detailed understanding of site hydrogeology and an extensive sampling network may be critical for the correct interpretation of monitored natural attenuation of MTBE.
Field Studies on the Fate and Transport of Pharmaceutical Residues in Bank Filtration
Authors: Heberer Thomas , Mechlinski Andy , Fanck Britta , Knappe Andrea , Massmann Gudrun , Pekdeger Asaf , Fritz Birgit
Published: February 2007

Bank filtration and artificial ground water recharge are important, effective, and cheap techniques for surface water treatment and removal of microbes, as well as inorganic, and some organic, contaminants. Nevertheless, physical, chemical, and biological processes of the removal of impurities are not understood sufficiently. A research project titled Natural and Artificial Systems for Recharge and Infiltration attempts to provide more clarity in the processes affecting the removal of these contaminants. The project focuses on the fate and transport of selected emerging contaminants during bank filtration at two transects in Berlin, Germany. Several detections of pharmaceutically active compounds (PhACs) in ground water samples from bank filtration sites in Germany led to furthering research on the removal of these compounds during bank filtration. In this study, six PhACs including the analgesic drugs diclofenac and propyphenazone, the antiepileptic drugs carbamazepine and primidone, and the drug metabolites clofibric acid and 1‐acetyl‐1‐methyl‐2‐dimethyl‐oxamoyl‐2‐phenylhydrazide were found to leach from the contaminated streams and lakes into the ground water. These compounds were also detected at low concentrations in receiving public supply wells. Bank filtration either decreased the concentrations by dilution (e.g., for carbamazepine and primidone) and partial removal (e.g., for diclofenac), or totally removed PhACs (e.g., bezafibrate, indomethacine, antibiotics, and estrogens). Several PhACs, such as carbamazepine and especially primidone, were readily transported during bank filtration. They are thought to be good indicators for evaluating whether surface water is impacted by contamination from municipal sewage effluent or whether contamination associated with sewage effluent can be transported into ground water at ground water recharge sites.
INVESTIGATION OF DYNAMICAL SYSTEMS USING SYMBOLIC IMAGES: EFFICIENT IMPLEMENTATION AND APPLICATIONS
Authors: AVRUTIN V. , LEVI P. , SCHANZ M. , FUNDINGER D. , OSIPENKO G.
Published: February 2007

Symbolic images represent a unified framework to apply several methods for the investigation of dynamical systems both discrete and continuous in time. By transforming the system flow into a graph, they allow it to formulate investigation methods as graph algorithms. Several kinds of stable and unstable return trajectories can be localized on this graph as well as attractors, their basins and connecting orbits. Extensions of the framework allow, e.g. the calculation of the Morse spectrum and verification of hyperbolicity. In this work, efficient algorithms and adequate data structures will be presented for the construction of symbolic images and some basic operations on them, like the localization of the chain recurrent set and periodic orbits. The performance of these algorithms will be analyzed and we show their application in practice. The focus is not only put on several standard systems, like Lorenz and Ikeda, but also on some less well-known ones. Additionally, some tuning techniques are presented for an efficient usage of the method.
DOUBLE-HOPF BIFURCATION IN AN OSCILLATOR WITH EXTERNAL FORCING AND TIME-DELAYED FEEDBACK CONTROL
Authors: CHEN ZHEN , YU PEI
Published: February 2007

In this paper, an oscillator with time delayed velocity feedback controls is studied in detail. Particular attention is given to internal double-Hopf bifurcation with an external exciting force. Linear analysis is used to find the critical conditions under which double-Hopf bifurcation occurs. Then center manifold theory is applied to obtain an ODE system described on a four-dimensional center manifold. Further, the technique of multiple-time scales is employed to find the approximate solutions of periodic and quasi-periodic motions. Finally, numerical simulation results are presented to not only validate the analytical predictions, but also show chaotic motions for some certain parameter values.
SHRIMP STRUCTURE AND ASSOCIATED DYNAMICS IN PARAMETRICALLY EXCITED OSCILLATORS
Authors: ZOU Y. , THIEL M. , ROMANO M. C. , KURTHS J. , BI Q.
Published: February 2007

We investigate the bifurcation structures in a two-dimensional parameter space (PS) of a parametrically excited system with two degrees of freedom both analytically and numerically. By means of the Rényi entropy of second order K2, which is estimated from recurrence plots, we uncover that regions of chaotic behavior are intermingled with many complex periodic windows, such as shrimp structures in the PS. A detailed numerical analysis shows that the stable solutions lose stability either via period doubling, or via intermittency when the parameters leave these shrimps in different directions, indicating different bifurcation properties of the boundaries. The shrimps of different sizes offer promising ways to control the dynamics of such a complex system.
PERIODIC CONSTANTS AND TIME-ANGLE DIFFERENCE OF ISOCHRONOUS CENTERS FOR COMPLEX ANALYTIC SYSTEMS
Authors: LIU YIRONG , LI JIBIN
Published: February 2007

By introducing a concept of the time-angle difference for planar complex analytic systems, two recursive formulas of the function of the time-angle difference and period constants of complex isochronous centers can be given. Using these results to a class of real cubic system, the first five period constants and the isochronous center conditions of the origin are obtained. One open problem posed by [Cairo et al., 1999] is proved.
Glucagon-like peptide-1 excites pancreas-projecting preganglionic vagal motoneurons
Authors: Wan S. , Coleman F. H. , Travagli R. A.
Published: February 2007

Glucagon-like peptide-1 (GLP-1) increases pancreatic insulin secretion via a direct action on pancreatic β-cells. A high density of GLP-1-containing neurons and receptors is also present in brain stem vagal circuits; therefore, the aims of the present study were to investigate 1) whether identified pancreas-projecting neurons of the dorsal motor nucleus of the vagus (DMV) respond to exogenously applied GLP-1, 2) the mechanism(s) of action of GLP-1, and 3) whether the GLP-1-responsive neurons (putative modulators of endocrine secretion) could be distinguished from DMV neurons responsive to peptides that modulate pancreatic exocrine secretion, specifically pancreatic polypeptide (PP). Whole cell recordings were made from identified pancreas-projecting DMV neurons. Perfusion with GLP-1 induced a concentration-dependent depolarization in ∼50% of pancreas-projecting DMV neurons. The GLP-1 effects were mimicked by exendin-4 and antagonized by exendin-(9–39). In ∼60% of the responsive neurons, the GLP-1-induced depolarization was reduced by tetrodotoxin (1 μM), suggesting both pre- and postsynaptic sites of action. Indeed, the GLP-1 effects were mediated by actions on potassium currents, GABA-induced currents, or both. Importantly, neurons excited by GLP-1 were unresponsive to PP and vice versa. These data indicate that 1) GLP-1 may act on DMV neurons to control pancreatic endocrine secretion, 2) the effects of GLP-1 on pancreas-projecting DMV neurons are mediated both via a direct excitation of their membrane as well as via an effect on local circuits, and 3) the GLP-1-responsive neurons (i.e., putative endocrine secretion-controlling neurons) could be distinguished from neurons responsive to PP (i.e., putative exocrine secretion-controlling neurons).
Interleukin-10 counteracts impaired endothelium-dependent relaxation induced by ANG II in murine aortic rings
Authors: Zemse Saiprasad M. , Hilgers Rob H. P. , Webb R. Clinton
Published: February 2007

ANG II stimulates the production of reactive oxygen species and activates proinflammatory cytokines leading to endothelial dysfunction. We hypothesized that the anti-inflammatory cytokine IL-10 counteracts the impairment in endothelium-dependent ACh relaxation caused by ANG II. Aortic rings of C57BL/6 mice were incubated in DMEM in the presence of vehicle (deionized H2O), ANG II (100 nmol/l), recombinant mouse IL-10 (300 ng/ml), or both ANG II and IL-10 for 22 h at 37°C. After incubation, rings were mounted in a wire myograph to assess endothelium-dependent vasorelaxation to cumulative concentrations of ACh. Overnight exposure of aortic rings to ANG II resulted in blunted ACh-induced vasorelaxation compared with that shown in untreated rings (maximal response = 44 ± 3% vs. 64 ± 3%, respectively; P < 0.05). IL-10 treatment significantly restored this impairment in relaxation (63 ± 2%). In addition, the NADPH oxidase inhibitor apocynin restored the impairment in relaxation (maximal response = 76 ± 3%). Western blotting showed increased gp91 phox expression (a subunit of NADPH oxidase) in response to ANG II. Vessels treated with a combination of ANG II and IL-10 showed decreased expression of gp91 phox. Immunohistochemical analysis showed increased gp91 phox expression in ANG II-treated vessels compared with those treated with combined ANG II and IL-10. We found that the anti-inflammatory cytokine IL-10 prevents impairment in endothelium-dependent vasorelaxation in response to long-term incubation with ANG II via decreasing NADPH oxidase expression.
Loss of TP53 in sarcomas with 17p12~p11 gain. A fine-resolution oligonucleotide array comparative genomic hybridization study
Authors: Kaur S. , Larramendy M.L. , Vauhkonen H. , Böhling T. , Knuutila S.
Published: February 2007

The amplification or gain of the p-arm of chromosome 17 is common in sarcomas, suggesting its role in carcinogenesis. Here, we report the architectural structure and targets of 17p aberrations commonly shared by osteosarcoma (OS), leiomyosarcoma (LMS) and malignant fibrous histiocytoma (MFH) of soft tissue. Two low-grade and two high-grade soft tissue LMS, three OS, and two MFH samples were studied using fine-resolution oligonucleotide-based microarray comparative genomic hybridization. Eight of the nine samples showed a loss of 17pter→p13, the locus of tumor suppressor TP53 preceding the amplified area 17p12→p11.2. The size and detailed architecture of the amplified region of 17p differed between the studied sarcoma entities. OS and high-grade LMS showed similar complex patterns of discontinuous amplifications with regions of gain in between. MFH and low-grade LMS showed continuous regions of gains and amplifications. Precise boundaries of the lost or gained regions were determined, and in addition to the previously suggested targets of the region, ELAC and FLCN were amplified in all the sarcoma entities.
Class I genes have split from the MHC in the tammar wallaby
Authors: Deakin J.E. , Siddle H.V. , Cross J.G.R. , Belov K. , Graves J.A.M.
Published: February 2007

Genes within the Major Histocompatibility Complex (MHC) are critical to the immune response and immunoregulation. Comparative studies have revealed that the MHC has undergone many changes throughout evolution yet in tetrapods the three different classes of MHC genes have maintained linkage, suggesting that there may be some functional advantage obtained by maintaining this clustering of MHC genes. Here we present data showing that class II and III genes, the antigen processing gene TAP2, and MHC framework genes are found together in the tammar wallaby on chromosome 2. Surprisingly class I loci were not found on chromosome 2 but were mapped to ten different locations spread across six chromosomes. This distribution of class I loci in the wallaby on nearly all autosomes is not a characteristic of all marsupials and may be a relatively recent phenomenon. It highlights the need for the inclusion of more than one marsupial species in comparative studies and raises questions regarding the functional significance of the clustering of MHC genes.
The Psychopathology of Posttraumatic Embitterment Disorders
Authors: Linden Michael , Baumann Kai , Rotter Max , Schippan Barbara
Published: February 2007

Background: The posttraumatic embitterment disorder (PTED) was introduced as a new subgroup of adjustment disorders. The trigger event in PTED is an exceptional, though normal negative life event that is experienced as a violation of basic beliefs and values. The predominant emotion in PTED is embitterment. This study presents first data on the psychopathological profile of PTED. Method: 48 inpatients were diagnosed by clinical judgment as suffering from PTED. Patients were then interviewed with the standardized Mini International Neuropsychiatric Interview (MINI) and an additional interview section on the diagnostic criteria for PTED. Patients also filled in the Symptom Checklist-90-Revision (SCL-90-R), and the Impact of Event Scale (IES-R). Results: According to the MINI68.8% of the patients fulfilled the criteria for adjustment disorders, 52.1% for major depression, 41.7% for dysthymia, and 35.4% for generalized anxiety disorders. 100% of patients reported that they were suffering from intrusive thoughts about the event. 97.9% of the patients complained about persistent negative mood, 91.7% about restlessness, 83.3% inhibition of drive and loss of interest, 77.1% phobic avoidance of places related to the event, and 75% resignation, but 91.7% reported normal mood when distracted. The SCL-90-R indicated a high load of general psychopathological complaints with an average positive symptom total score of 52.26. Characteristic were feelings of injustice (100%), embitterment (97.7%), and rage (91.7%). The IES-R scale indicated a high prevalence of posttraumatic stress, with an average total score of 3.23. The average duration of illness was 31.7 months. Conclusions: The PTED patients are suffering from severe, multiform, and disabling symptoms. Their clinical features pose difficult diagnostic problems. The predominant complaints about feelings of injustice, embitterment, and rage and the results of the IES speak for the importance of the critical event for the development and understanding of such disorders.
Exclusion of Serum- and Glucocorticoid-Induced Kinase 1 (SGK1) as a Candidate Gene for Genetically Heterogeneous Renal Pseudohypoaldosteronism Type I in Eight Families
Authors: Riepe Felix G. , Holterhus Paul-Martin
Published: February 2007

Objective: Autosomal-dominant pseudohypoaldosteronism type 1 (PHA1) is mostly caused by mutations in the mineralocorticoid receptor (NR3C2) gene. However, several kindreds with clinical signs of PHA1 but without NR3C2 gene mutations or deletions are reported. Serum- and glucocorticoid-induced kinase 1 (Sgk1) is involved in epithelial sodium reabsorption by facilitating the accumulation of the epithelial sodium channel in the plasma membrane. Therefore variations in the SGK1 gene may aggravate renal salt loss or cause PHA1. Methods: The SGK1 genewas sequenced in 10 patients with the typical clinical signs of PHA1 but without NR3C2 or SCNN1A, SCNN1B and SCNN1C gene mutation. Results: No disease-causing SGK1 gene mutation was detected in the studied PHA1 patient group. Two novel intronic SNPs which were also present in the normal population were detected in 2 patients. Conclusion: Our data do not support that SGK1 gene variations are disease-causing factors in genetically unexplained PHA1. Therefore, systematic investigation of other factors downstream of the MR involved in epithelial sodium reabsorption is warranted in patients with autosomal-dominant PHA1.
An Essential Role for gp130 in Neointima Formation Following Arterial Injury
Authors: Wang Dong , Liu Zhimin , Li Quanyi , Karpurapu Manjula , Kundumani-Sridharan Venkatesh , Cao Huiqing , Dronadula Nagadhara , Rizvi Farhan , Bajpai Arun K. , Zhang Chunxiang , Müller-Newen Gerhard , Harris Kevin W. , Rao Gadiparthi N.
Published: February 2007

Interleukin (IL)-6 induced vascular smooth muscle cell (VSMC) motility in a dose-dependent manner. In addition, IL-6 stimulated tyrosine phosphorylation of gp130, resulting in the recruitment and activation of STAT-3. IL-6–induced VSMC motility was found to be dependent on activation of gp130/STAT-3 signaling. IL-6 also induced cyclin D1 expression in a time- and gp130/STAT-3–dependent manner in VSMCs. Suppression of cyclin D1 levels via the use of its small interfering RNA molecules inhibited IL-6–induced VSMC motility. Furthermore, balloon injury induced IL-6 expression both at mRNA and protein levels in rat carotid artery. Balloon injury also caused increased STAT-3 phosphorylation and cyclin D1 expression, leading to smooth muscle cell migration from the media to the intimal region. Blockade of gp130/STAT-3 signaling via adenovirus-mediated expression of dngp130 or dnSTAT-3 attenuated balloon injury–induced STAT-3 phosphorylation and cyclin D1 induction, resulting in reduced smooth muscle cell migration from media to intima and decreased neointima formation. Together, these observations for the first time suggest that IL-6/gp130/STAT-3 signaling plays an important role in vascular wall remodeling particularly in the settings of postangioplasty and thereby in neointima formation.
Cognitive Status, Stroke Symptom Reports, and Modifiable Risk Factors Among Individuals With No Diagnosis of Stroke or Transient Ischemic Attack in the
RE
asons for
G
eographic and
R
acial
D
ifferences in
S
troke (REGARDS) Study
Authors: Wadley Virginia G. , McClure Leslie A. , Howard Virginia J. , Unverzagt Frederick W. , Go Rodney C. , Moy Claudia S. , Crowther Martha R. , Gomez Camilo R. , Howard George
Published: February 2007

Background and Purpose—

Vascular disorders that increase risk for stroke may be accompanied by decrements in cognitive functioning and by stroke symptoms in the absence of diagnosed stroke or transient ischemic attack. This study evaluates relationships among cognitive status, stroke symptom reports, and cardiovascular and behavioral factors.

Methods—

RE
asons for
G
eographic and
R
acial
D
ifferences in
S
troke (REGARDS), a prospective population study of stroke incidence, assesses stroke risk with telephone interviews and in-home physicals. Excluding subjects with a history of stroke or transient ischemic attack, this analysis includes 14 566 black and white men and women ≥45 years of age. Incremental logistic models examine baseline relationships among cognitive status (Six-item Screener scores), stroke symptom reports, demographics, health behaviors, cardiovascular indices, and depressive symptoms.

Results—

A history of stroke symptoms was related to impaired cognitive status after adjusting for age, gender, race, and education but not after adjusting for poor health behaviors, vascular risk factors, and depressive symptoms. Odds of experiencing a stroke symptom increased 35% with each of five modifiable factors (hypertension, diabetes, smoking, lack of exercise, depressive symptoms), and odds of cognitive impairment increased an additional 12% with each modifiable factor. Lifelong abstinence from alcohol, lack of exercise, and depressive symptoms were independently related to impaired cognitive status.

Conclusions—

The increased likelihood of cognitive impairment among subjects reporting stroke symptoms in the absence of a diagnosed stroke or transient ischemic attack suggests that such symptoms are not benign and may warrant clinical evaluation that includes a cognitive assessment. Future studies that include brain imaging may clarify the etiology of these symptoms.
Endovascular Recanalization of Basilar Artery Occlusion 80 Days After Symptom Onset
Authors: Yu Wengui , Kostanian Varoujan , Fisher Mark
Published: February 2007

Background and Purpose—

Acute basilar artery occlusion portends high risk of stroke and death. Thrombolysis or endovascular therapy has been limited to patients who present within hours of symptom onset. Without recanalization, acute basilar artery occlusion almost always results in death or severe disability.

Summary of Case—

We report a case of basilar artery occlusion and successful endovascular recanalization 80 days after symptom onset.

Conclusions—

Endovascular therapy can be feasible and safe for symptomatic basilar artery occlusion at chronic stage.
Human Pharmacokinetics and Interconversion of Enantiomers of MK‐0767, a Dual PPARα/γ Agonist
Authors: Rippley Ronda K. , Yan Kerri X. , Matthews Natalie D. , Greenberg Howard E. , Herman Gary A. , Wagner John A.
Published: February 2007

MK‐0767, a dual peroxisome proliferator‐activated receptor (PPAR) α/γ agonist, has been studied as a potential treatment of type 2 diabetes and dyslipidemia. The pharmacokinetics and interconversion of (+)‐(R)‐MK‐0767 and (−)‐(S)‐MK‐0767 were evaluated following oral administration of each single enantiomer and the racemate to healthy subjects. The results demonstrate that, consistent with in vitro experiments, chiral inversion occurs rapidly in vivo, and interconversion equilibrium favors (+)‐(R). After all treatments, a stable ratio (R/S) of 2 to 2.5 was achieved within 8 hours in most individuals, congruent with model‐based estimates of interconversion half‐life. In addition, the pharmacokinetics of each enantiomer were generally similar regardless of treatment. Modeling and simulation of enantiomer disposition suggest that the observed predominance of (+)‐(R)‐MK‐0767 in plasma may result from differential volumes of distribution between (−)‐(S) and (+)‐(R), preferential conversion from (−)‐(S) to (+)‐(R), or a combination of these, but not faster clearance of (−)‐(S) compared to (+)‐(R).
Interferon-producing killer dendritic cells (IKDCs) arise via a unique differentiation pathway from primitive c-kitHiCD62L+ lymphoid progenitors
Authors: Welner Robert S. , Pelayo Rosana , Garrett Karla P. , Chen Xinrong , Perry S. Scott , Sun Xiao-Hong , Kee Barbara L. , Kincade Paul W.
Published: February 2007

Interferon-producing killer dendritic cells (IKDCs) have only recently been described and they share some properties with plasmacytoid dendritic cells (pDCs). We now show that they can arise from some of the same progenitors. However, IKDCs expressed little or no RAG-1, Spi-B, or TLR9, but responded to the TLR9 agonist CpG ODN by production of IFNγ. The RAG-1−pDC2 subset was more similar to IKDCs than RAG-1+ pDC1s with respect to IFNγ production. The Id-2 transcriptional inhibitor was essential for production of IKDCs and natural killer (NK) cells, but not pDCs. IKDCs developed from lymphoid progenitors in culture but, unlike pDCs, were not affected by Notch receptor ligation. While IKDCs could be made from estrogen-sensitive progenitors, they may have a slow turnover because their numbers did not rapidly decline in hormone-treated mice. Four categories of progenitors were compared for IKDC-producing ability in transplantation assays. Of these, Lin−Sca-1+c-KitHiThy1.1−L-selectin+ lymphoid progenitors (LSPs) were the best source. While NK cells resemble IKDCs in several respects, they develop from different progenitors. These observations suggest that IKDCs may arise from a unique differentiation pathway, and one that diverges early from those responsible for NK cells, pDCs, and T and B cells.
Expression of oncogenic K-ras from its endogenous promoter leads to a partial block of erythroid differentiation and hyperactivation of cytokine-dependent signaling pathways
Authors: Zhang Jing , Liu Yangang , Beard Caroline , Tuveson David A. , Jaenisch Rudolf , Jacks Tyler E. , Lodish Harvey F.
Published: February 2007

When overexpressed in primary erythroid progenitors, oncogenic Ras leads to the constitutive activation of its downstream signaling pathways, severe block of terminal erythroid differentiation, and cytokine-independent growth of primary erythroid progenitors. However, whether high-level expression of oncogenic Ras is required for these phenotypes is unknown. To address this issue, we expressed oncogenic K-ras (K-rasG12D) from its endogenous promoter using a tetracycline-inducible system. We show that endogenous K-rasG12D leads to a partial block of terminal erythroid differentiation in vivo. In contrast to results obtained when oncogenic Ras was overexpressed from retroviral vectors, endogenous levels of K-rasG12D fail to constitutively activate but rather hyperactivate cytokine-dependent signaling pathways, including Stat5, Akt, and p44/42 MAPK, in primary erythroid progenitors. This explains previous observations that hematopoietic progenitors expressing endogenous K-rasG12D display hypersensitivity to cytokine stimulation in various colony assays. Our results support efforts to modulate Ras signaling for treating hematopoietic malignancies.
Blast sampling for structural and functional analyses
Authors: Friedrich Anne , Ripp Raymond , Garnier Nicolas , Bettler Emmanuel , Deléage Gilbert , Poch Olivier , Moulinier Luc
Published: February 2007

Background

The post-genomic era is characterised by a torrent of biological information flooding the public databases. As a direct consequence, similarity searches starting with a single query sequence frequently lead to the identification of hundreds, or even thousands of potential homologues. The huge volume of data renders the subsequent structural, functional and evolutionary analyses very difficult. It is therefore essential to develop new strategies for efficient sampling of this large sequence space, in order to reduce the number of sequences to be processed. At the same time, it is important to retain the most pertinent sequences for structural and functional studies.

Results

An exhaustive analysis on a large scale test set (284 protein families) was performed to compare the efficiency of four different sampling methods aimed at selecting the most pertinent sequences. These four methods sample the proteins detected by BlastP searches and can be divided into two categories: two customisable methods where the user defines either the maximal number or the percentage of sequences to be selected; two automatic methods in which the number of sequences selected is determined by the program. We focused our analysis on the potential information content of the sampled sets of sequences using multiple alignment of complete sequences as the main validation tool. The study considered two criteria: the total number of sequences in BlastP and their associated E-values. The subsequent analyses investigated the influence of the sampling methods on the E-value distributions, the sequence coverage, the final multiple alignment quality and the active site characterisation at various residue conservation thresholds as a function of these criteria.

Conclusion

The comparative analysis of the four sampling methods allows us to propose a suitable sampling strategy that significantly reduces the number of homologous sequences required for alignment, while at the same time maintaining the relevant information concerning the active site residues.
iCartiGD: the Integrated Cartilage Gene Database
Authors: Yeung Ming-Yiu , Smith David K , Chan Matthew SY , Li Cheuk M , Wong Brian C , Cheung Kenneth MC , Luk Keith DK , Cheah Kathryn SE , Sham Pak , Chan Danny , Song You-Qiang
Published: February 2007

Background

Diseases of cartilage, such as arthritis and degenerative disc disease, affect the majority of the general population, particularly with ageing. Discovery and understanding of the genes and pathways involved in cartilage biology will greatly assist research on the development, degeneration and disorders of cartilage.

Description

We have established the Integrated Cartilage Gene Database (iCartiGD) of genes that are known, based on results from high throughput experiments, to be expressed in cartilage. Information about these genes is extracted automatically from public databases and presented as a single page report via a web-browser. A variety of flexible search options are provided and the chromosomal distribution of cartilage associated genes can be presented.

Conclusion

iCartiGD provides a comprehensive source of information on genes known to be expressed in cartilage. It will remain current due to its automatic update capability and provide researchers with an easily accessible resource for studies involving cartilage. Genetic studies of the development and disorders of cartilage will benefit from this database.
Interleukin-4 inhibition of interleukin-1-induced expression of matrix metalloproteinase-3 (MMP-3) is independent of lipoxygenase and PPARγ activation in human gingival fibroblasts
Authors: Stewart Denise , Javadi Masoud , Chambers Mariah , Gunsolly Chad , Gorski Grzegorz , Borghaei Ruth C
Published: February 2007

Background

Interleukin 4 (IL-4) has been shown to suppress interleukin-1 (IL-1) induced expression of matrix metalloproteinase-3 (MMP-3) in human synovial and gingival fibroblasts, but the mechanism of suppression has not been determined. Activators of peroxisome proliferator-activated receptor-γ (PPARγ) have been shown to inhibit cytokine induced expression of MMPs in other cell types, and IL-4 has been shown to activate PPARγ by stimulating production of ligands through the lipoxygenase pathway. It has been suggested that PPARγ may inhibit expression of MMPs by competing with transcription factor AP-1 for binding to a putative composite binding element in the promoters. The objective of this study was to determine whether the suppressive effects of IL-4 on the IL-1 induced expression of MMP-3 involve activation of lipoxygenase and/or PPARγ.

Results

Western blotting revealed the presence of PPARγ in nuclear extract of HGF. IL-1 induced binding of nuclear extract to the putative composite PPRE/AP-1 site was diminished in the presence of pioglitazone, but there was no evidence of any change in the composition of the retarded complexes, and no evidence of PPARγ binding to this site. Nordihydroguaiaretic acid (NDGA), a non-selective lipoxygenase inhibitor, and MK886, a specific inhibitor of 5-lipoxygenase, induced MMP-3 expression synergistically with IL-1. However IL-4 was still able to inhibit MMP-3 expression in the presence of NDGA or MK886 and IL-1. Activation of PPARγ with pioglitazone not only failed to inhibit IL-1 induced expression of MMP-3 mRNA, but rather super-induced MMP-3 in the presence of IL-1. PPARγ antagonist GW9662 failed to abolish the suppressive effects of IL-4. Another PPARγ activator, 15-deoxy-Delta12,14prostaglandin J2 (15dPGJ2), also super-induced MMP-3 mRNA, and this was due at least in part to increased transcription.

Conclusion

IL-4 suppression of IL-1-induced MMP-3 expression in HGF is independent of lipoxygenase activity and activation of PPARγ. Super-induction of MMP-3 by pioglitazone may have important implications for patients using pioglitazone to treat type II diabetes in the presence of chronic inflammation.
Tax Reform Unraveling
Authors: Graetz Michael J
Published: February 2007

The Tax Reform Act of 1986 was widely heralded as the most significant change in our nation's tax law since the income tax was extended to the masses during World War II. It was the crowning domestic policy achievement of President Ronald Reagan, who proclaimed it “the best antipoverty measure, the best pro-family measure, and the best job-creation measure ever to come out of the Congress of the United States.” The law's rate reductions and base broadening reforms were mimicked throughout the countries belonging to the OECD. Even at the time, however, reading the paeans to this legislation was like watching a Tennessee Williams play: something was terribly wrong, but nobody was talking about it. Two decades later, the changes wrought by the 1986 act have proven neither revolutionary nor stable. Tax experts now regard the 1986 act as a promise failed. The public seems to agree, and considerable public support exists for a “flat tax” or a national sales tax to replace the income tax. I shall examine the most important individual and corporate income tax changes since 1986, before turning to proposals for restructuring the nation's tax system.
Combination Inhaled Bronchodilator Therapy in the Management of Chronic Obstructive Pulmonary Disease
Authors: Nichols Jake
Published: February 2007

The Global Obstructive Lung Disease (GOLD) guidelines suggest the potential use of combination bronchodilator therapy in patients with stage II or higher chronic obstructive pulmonary disease (COPD). Guidelines from the American Thoracic Society also mention that certain combinations of bronchodilators may prevent exacerbations. Combinations of several agents may benefit patients with COPD not only by improving lung function, but also by decreasing exacerbation rates and improving overall symptoms. A MEDLINE search was conducted to gather published data and clinical trial reports regarding the clinical effect of combining bronchodilators in the treatment of COPD. Agents such as oxitropium, which is not available in the United States, were not included in the analysis. Although the data are somewhat limited, trials suggest many potential benefits for combination bronchodilator therapy in patients with COPD. Information on combining long‐acting anticholinergic drugs with long‐acting β2‐agonists is scarce, but the combination of two long‐acting agents may provide additional benefits by improving patient compliance with prescribed regimens. More studies evaluating outcomes in patients with COPD may help solidify the potential benefits of combination inhaled bronchodilator therapy.
Gene Expression Analysis of Hematopoietic Progenitor Cells Identifies Dlg7as a Potential Stem Cell Gene
Authors: Gudmundsson Kristbjorn Orri , Thorsteinsson Leifur , Sigurjonsson Olafur E. , Keller Jonathan R. , Olafsson Karl , Egeland Torstein , Gudmundsson Sveinn , Rafnar Thorunn
Published: February 2007

Inducible hematopoietic stem/progenitor cell lines represent a model for studying genes involved in self-renewal and differentiation. Here, gene expression was studied in the inducible human CD34+ acute myelogenous leukemia cell line KG1 using oligonucleotide arrays and suppression subtractive cloning. Using this approach, we identified Dlg7, the homolog of the Drosophila Dlg1 tumor suppressor gene, as downregulated at the early stages of KG1 differentiation. Similarly, Dlg7 was expressed in normal purified umbilical cord blood CD34+CD38− progenitors but not in the more committed CD34+CD38+ population. Dlg7 expression was not detected in differentiated cells obtained from hematopoietic colonies, nor was expression detected in purified T-cells, B-cells, and monocytes. When analyzed in different types of stem cells, Dlg7 expression was detected in purified human bone marrow-derived CD133+ progenitor cells, human mesenchymal stem cells, and mouse embryonic stem (ES) cells. Overexpression of Dlg7 in mouse ES cells increased their growth rate and reduced the number of EBs emerging upon differentiation. In addition, the EBs were significantly smaller, indicating an inhibition in differentiation. This inhibition was further supported by higher expression of Bmp4, Oct4, Rex1, and Nanog in EBs overexpressing Dlg7 and lower expression of Brachyury. Finally, the Dlg7 protein was detected in liver and colon carcinoma tumors but not in normal adjacent tissues, suggesting a role for the gene in carcinogenesis. In conclusion, our results suggest that Dlg7 has a role in stem cell survival, in maintaining stem cell properties, and in carcinogenesis.

Disclosure of potential conflicts of interest is found at the end of this article.
Analyses of Very Early Hemopoietic Regeneration After Bone Marrow Transplantation: Comparison of Intravenous and Intrabone Marrow Routes
Authors: Li Qing , Hisha Hiroko , Yasumizu Ryoji , Fan Tian-Xue , Yang Guo-Xiang , Li Qiang , Cui Yun-Ze , Wang Xiao-Li , Song Chang-Ye , Okazaki Satoshi , Mizokami Tomomi , Cui Wen-Hao , Guo Kequan , Li Ming , Feng Wei , Katou Junko , Ikehara Susumu
Published: February 2007

In bone marrow transplantation (BMT), bone marrow cells (BMCs) have traditionally been injected intravenously. However, remarkable advantages of BMT via the intra-bone-marrow (IBM) route (IBM-BMT) over the intravenous route (IV-BMT) have been recently documented by several laboratories. To clarify the mechanisms underlying these advantages, we analyzed the kinetics of hemopoietic regeneration after IBM-BMT or IV-BMT in normal strains of mice. At the site of the direct injection of BMCs, significantly higher numbers of donor-derived cells in total and of c-kit+ cells were observed at 2 through 6 days after IBM-BMT. In parallel, significantly higher numbers of colony-forming units in spleen were obtained from the site of BMC injection. During this early period, higher accumulations of both hemopoietic cells and stromal cells were observed at the site of BMC injection by the IBM-BMT route. The production of chemotactic factors, which can promote the migration of a BM stromal cell line, was observed in BMCs obtained from irradiated mice as early as 4 hours after irradiation, and the production lasted for at least 4 days. In contrast, sera collected from the irradiated mice showed no chemotactic activity, indicating that donor BM stromal cells that entered systemic circulation cannot home effectively into recipient bone cavity. These results strongly suggest that the concomitant regeneration of microenvironmental and hemopoietic compartments in the marrow (direct interaction between them at the site of injection) contributes to the advantages of IBM-BMT over IV-BMT.

Disclosure of potential conflicts of interest is found at the end of this article.
Enhanced Oxide Ion Conductivity in Stabilized δ‐Bi2O3.
Authors: Punn Rita , Feteira Antonio M. , Sinclair Derek C. , Greaves Colin
Published: February 2007

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis and cellular uptake of a MR contrast agent coupled to an antisense peptide nucleic acid – cell– penetrating peptide conjugate
Authors: Su W. , Mishra R. , Pfeuffer J. , Wiesmüller K.‐H. , Ugurbil K. , Engelmann J.
Published: February 2007

In order to image mRNA transcription by in vivo magnetic resonance imaging (MRI), two intracellular MR contrast agents were developed, which are composed of a Gd–DOTA complex, a peptide nucleic acid (PNA) sequence and a cell‐penetrating peptide. One was designed to bind to mRNA of dsRed (red fluorescent protein originating from Discosoma coral) by its PNA sequence, whereas the second one contains a nonsense sequence with no natural counterpart. The conjugates were synthesized using a continuous solid‐phase synthesis scheme and characterized by ESI‐MS. Fluorescence studies showed that both contrast agents could enter efficiently into 3T3 cells in a concentration‐dependent manner from 0.5 to 9.0 µM. The contrast agent was located predominantly in vesicles around the nucleus, whereas no uptake into the nucleus was observed. The results of in vitro MR studies showed a statistically significant increase of the intracellular relaxation rate R
1,cell at a labeling concentration of only 0.5 µM, thus contrast enhancement was detectable too. These results suggest that the synthesized contrast agents could label cells for optical as well as MR imaging and in future might be useful to prove specific accumulation in cells containing target mRNA. Copyright © 2007 John Wiley & Sons, Ltd.
Single‐injection ornithine decarboxylase‐directed antisense therapy using atelocollagen to suppress human cancer growth
Authors: Nakazawa Kunihiko , Nemoto Takahiro , Hata Tomoko , Seyama Yousuke , Nagahara Shunji , Sano Akihiko , Itoh Hiroshi , Nagai Yutaka , Kubota Shunichiro
Published: February 2007

BACKGROUND

Substantial evidence supports a direct role of ornithine decarboxylase (ODC) in the development and maintenance of human tumors. Although antisense oligonucleotide therapy targeting various genes are useful for cancer treatment, 1 of the major limitations is the problem of delivery. A novel antisense oligonucleotide delivery method is described that allows prolonged sustainment and release of ODC antisense oligonucleotides in vivo using atelocollagen.

METHODS

The effect of ODC antisense oligonucleotides in the atelocollagen on cell growth of gastrointestinal cancer (MKN 45 and COLO201) and rhabdomyosarcoma (RD) was studied in vitro using a cell‐counting method with a hemocytometer. In vivo, the effect of intratumoral, intramuscular, and intraperitoneal single administration of ODC antisense oligonucleotides in the atelocollagen on tumor growth of MKN45, COLO201, and RD cells was studied. ODC activity and polyamine contents were measured.

RESULTS

In vitro, ODC antisense oligonucleotides in the atelocollagen remarkably suppressed MKN45, COLO201, and RD cell growth. A single administration of antisense oligonucleotides in the atelocollagen via 3 routes remarkably suppressed the growth of MKN45, COLO201, and RD tumor over a period of 35–42 days.

CONCLUSIONS

As various human cancers significantly express ODC, the results strongly suggest that this new antisense method may be of considerable value for treatment of human cancers. Cancer 2007;109:993–1002. © 2007 American Cancer Society.
Analysis of saturated free fatty acids from pollen by HPLC with fluorescence detection
Authors: You Jinmao , Zhu Fang , Zhao Wenchen , Zhao Xian'en , Suo Yourui , Liu Sujuan
Published: February 2007

A sensitive method for the determination of free fatty acids using 2‐(2‐(anthracen‐10‐yl)‐1H‐naphtho[2,3‐d]imidazol‐1‐yl) ethyl‐p‐toluenesulfonate (ANITS) as tagging reagent with fluorescence detection has been developed. ANITS could easily and quickly label fatty acids in the presence of the K2CO3 catalyst at 90 °C for 40 min in N,N‐dimethylformamide solvent. From the extracts of rape bee pollen samples, 20 free fatty acids were sensitively determined. Fatty acid derivatives were separated on a reversed‐phase Eclipse XDB‐C8 column by HPLC in conjunction with gradient elution. The corresponding derivatives were identified by post‐column APCI/MS in positive‐ion detection mode. ANITS‐fatty acid derivatives gave an intense molecular ion peak at m/z [M+H]+; with MS/MS analysis, the collision‐induced dissociation spectra of m/z [M+H]+ produced the specific fragment ions at m/z [M–345]+ and m/z 345.0 (here, m/z 345 is the core structural moiety of the ANITS molecule). The fluorescence excitation and emission wavelengths of the derivatives were λex = 250 nm and λem = 512 nm, respectively. Linear correlation coefficients for all fatty acid derivatives are >0.9999. Detection limits, at a signal‐to‐noise ratio of 3 : 1, are 24.76–98.79 fmol for the labeled fatty acids.
A Convenient Preparative Method for New 1,3‐Bis(hetaryl)‐2‐chloropropen‐1‐ones Using β‐Alkoxy‐α‐chloroalkenyllithium Compounds
Authors: Itoh Akinori , Sakai Miho , Yoshimatsu Mitsuhiro
Published: February 2007

The 1,3‐biaryl and 1,3‐bis(hetaryl)propen‐1‐ones 14a–e, 16, 17a–c, 19, 20a and the corresponding acetals 15a–d, 18a and 21a–d were successfully synthesized by a stepwise process: the reaction of α‐chloro‐β‐ethoxyethenyllithium compounds and aldehydes and ketones, and the successive hydration with TMSOTf. Further palladium‐catalyzed arylation of 1,3‐biaryl‐2‐chloroprop‐2‐enones proceeded with good yields.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Book review
Authors: Bierman Leonard
Published: February 2007

Thomas L. Friedman. (2005; updated and expanded in 2006). The World Is Flat: A Brief History of the Twenty‐First Century. New York: Farrar, Straus and Giroux. 496 pages.
Book review
Authors: Bonin Michael E.
Published: February 2007

Ralph Christenson. (2006). Roadmap to Strategic HR. New York: AMACOM. 270 pages.
Book review
Authors: Chesley Julie
Published: February 2007

Gene Klann. (2003). Crisis Leadership: Using Military Lessons, Organizational Experiences, and the Power of Influence to Lessen the Impact of Chaos on the People You Lead. Greensboro, NC: Center for Creative Leadership Press. 85 pages.