bluuebunny/crossref_metadata_2025 huggingface dataset:
Air pollution and exhaled nitric oxide in Dutch schoolchildren
Authors: Graveland Haitske , Van Roosbroeck Sofie A H , Rensen Wilhelmina M , Brunekreef Bert , Gehring Ulrike
Published: November 2010

Background

Short-term changes in air pollution exposure in children may be associated with transient increases in exhaled nitric oxide (NO), a marker of airway inflammation. Also, children living in areas with high air pollution levels and/or high traffic densities appear to have chronically increased levels of exhaled NO. No studies have simultaneously addressed the long-term and short-term associations between traffic-related air pollution and exhaled NO.

Objectives

To investigate associations between exhaled NO in school children and both short-term changes in outdoor PM10and long-term traffic exposures.

Methods

Offline exhaled NO measurements were conducted in 812 children from nine Dutch schools within 400 m of motorways. Daily levels of particulate matter with a 50% cut-off aerodynamic diameter of 10 μm (PM10) were obtained from background monitoring stations. Long-term exposure to traffic-related air pollution was assessed using specific traffic-related characteristics such as total, car and truck motorway traffic and the distances of the children's homes and schools from the motorway.

Results

A positive association was found between ambient PM10concentrations on the day of exhaled NO measurement and exhaled NO (adjusted geometric means ratio (95% CI) 2.24 (1.37 to 3.65)) over the range of daily PM10concentrations of 44 μg/m3), which was largely attributable to a pollution peak associated with high particulate matter emissions from traditional Easter fires. There were suggestive associations between exhaled NO and traffic counts only in children with asthma, which were not statistically significance.

Conclusions

Short-term changes in ambient PM10largely attributable to biomass burning are associated with increased levels of exhaled NO.
Effects of copper, cadmium, lead, and arsenic in a live diet on juvenile fish growth
Authors: Erickson Russell J. , Mount David R. , Highland Terry L. , Hockett J. Russell , Leonard Edward N. , Mattson Vincent R. , Dawson Timothy D. , Lott Kevin G.
Published: November 2010

The effects of diet-borne copper, cadmium, lead, and arsenic on juvenile fish were evaluated using a live diet consisting of the oligochaete Lumbriculus variegatus . In 30 d exposures, no effects were observed on the growth and survival of rainbow trout ( Oncorhynchus mykiss ), fathead minnow ( Pimephales promelas ), and channel catfish ( Ictalurus punctatus ) fed diets contaminated with copper [130–310 µg Cu·(g dm)−1], cadmium [90–540 µg Cd·(g dm)−1], and lead [850–1000 µg Pb·(g dm)−1]. However, rainbow trout growth was reduced in a dose-dependent manner for diets contaminated with arsenic [26–77 µg As·(g dm)−1]. These effects of arsenic on fish growth were accompanied by slower feeding rate, reduced food conversion efficiency, liver cell abnormalities, and fecal matter changes suggestive of digestive effects, and occurred to a similar extent whether the diet was exposed to arsenate or arsenite. Effects from these dietary levels of arsenic, and the absence of effects from these dietary levels of metals, were generally consistent with literature reports using laboratory diets amended with toxicant salts. These results also indicated that reported growth effects on rainbow trout fed diets of invertebrates collected from mining-contaminated areas of the Clark Fork River (Montana, USA) or exposed in the laboratory to Clark Fork River sediments are likely more attributable to the arsenic than the metals in those diets.
The effect of flow regime on the occurrence of interference and exploitative competition in a salmonid species, white-spotted char (Salvelinus leucomaenis)
Authors: Hasegawa Koh , Yamamoto Shoichiro
Published: November 2010

We examined the effect of flow regime on the occurrence of interference and exploitative competition in a salmonid species, white-spotted char ( Salvelinus leucomaenis ). In the lotic treatment, char showed typical consequences of interference competition (i.e., fish aggressively defended their foraging positions, and individuals occupying the most profitable positions grew fastest). In the lentic treatment, however, char behavior was consistent with exploitative competition; fish cruised over a larger area in search of food resources and showed limited aggression and no evidence of a dominance hierarchy. Our results indicate that white-spotted char showed interference competition more commonly than exploitative competition in the lotic habitat and vice versa in the lentic habitat.
Testing the environmental prediction hypothesis for mast-seeding in California oaks
Authors: Koenig Walter D. , Knops Johannes M.H. , Carmen William J.
Published: November 2010

We analyzed 29 years of acorn production by five species of California oaks (genus Quercus ) to test the hypothesis that trees produce large seed crops prior to wet years, conditions facilitating seedling germination and survival. The mean crop of three of the species correlated positively and nontrivially with the following year’s rainfall, but none was statistically significant. Including the acorn crop 1 and 2 years earlier yielded several significant relationships between the acorn crop and future rainfall, but none held up when applied to a second, independent site. Across individuals, acorn production by 7% of trees correlated significantly with subsequent rainfall. Although these trees differed from other trees in several characters, differences were not sufficient to discriminate between trees that correlated significantly with subsequent rainfall from those that did not. We conclude that acorn production by California oaks does not forecast wet years and does not support the environmental prediction hypothesis.
Genetic adaptation of aspen (Populus tremuloides) populations to spring risk environments: a novel remote sensing approach
Authors: Li Haitao , Wang Xianli , Hamann Andreas
Published: November 2010

This study investigates geographic patterns of genetic variation in aspen (Populus tremuloides Michaux.) spring phenology with the aim of understanding adaptation of populations to climatic risk environments and the practical application of guiding seed transfer. We use a classical common garden experiment to reveal genetic differences among populations from western Canada and Minnesota, and we present a novel method to seamlessly map heat-sum requirements from remotely sensed green-up dates. Both approaches reveal similar geographic patterns: we find low heat-sum requirements in northern and high-elevation aspen populations, allowing them to take full advantage of a short growing season. High heat-sum requirements were found in populations from the central boreal plains of Saskatchewan and Alberta, and populations from Minnesota exhibit moderately low heat-sum requirements for budbreak. Analysis of corresponding climate normal data shows that late budbreak is strongly associated with the driest winter and spring environments, which suggests selection pressures for late budbreak due to both frost and drought risks in early spring. We therefore caution against long-distance seed transfer of Minnesota provenances to the boreal plains of Alberta and Saskatchewan. Although such transfers have been shown to increase tree growth in short-term field tests, this planting material may be susceptible to exceptional spring droughts.
Forest carbon stocks in Newfoundland boreal forests of harvest and natural disturbance origin II: model evaluation
Authors: Moroni M. T. , Shaw C. H. , Kurz W. A. , Rampley G. J.
Published: November 2010

The Intergovernmental Panel on Climate Change recommends that countries that use advanced (Tier 3) models to meet their international reporting obligations on forest greenhouse gas emissions and removals evaluate model predictions against independent field data. Unfortunately, estimates of total ecosystem C stocks and stock changes are scarce and consequently the recommended evaluations are rarely completed. The Carbon Budget Model of the Canadian Forest Sector (CBM-CFS3) is the core model of Canada’s National Forest Carbon Monitoring, Accounting, and Reporting System that implements an Intergovernmental Panel on Climate Change Tier 3 approach. It accounts for biomass, dead organic matter, and soil C pools as affected by natural and anthropogenic disturbances. We used data from a recent study of total ecosystem C stocks for black spruce ( Picea mariana (Mill.) BSP) and balsam fir ( Abies balsamea (L.) Mill.) boreal forest chronosequences of different disturbance origins in Newfoundland, Canada, to evaluate C stock and stock change predictions from the CBM-CFS3. Results indicated that the accuracy of the CBM-CFS3 is high for landscape-scale estimation of C stocks. Comparison of estimates stratified by lead species or disturbance type indicated that model accuracy could be improved at finer scales by increasing specific model parameters such as the snag fall rate and woody debris decay rates relative to default parameters.
ON SCALAR HYPERBOLIC CONSERVATION LAWS WITH A DISCONTINUOUS FLUX
Authors: BULÍČEK MIROSLAV , GWIAZDA PIOTR , MÁLEK JOSEF , ŚWIERCZEWSKA-GWIAZDA AGNIESZKA
Published: November 2010

We study the Cauchy problem for scalar hyperbolic conservation laws with a flux that can have jump discontinuities. We introduce new concepts of entropy weak and measure-valued solution that are consistent with the standard ones if the flux is continuous. Having various definitions of solutions to the problem, we then answer the question what kind of properties the flux should possess in order to establish the existence and/or uniqueness of solution of a particular type. In any space dimension we establish the existence of measure-valued entropy solution for a flux having countable jump discontinuities. Under the additional assumption on the Hölder continuity of the flux at zero, we prove the uniqueness of entropy measure-valued solution, and as a consequence, we establish the existence and uniqueness of weak entropy solution. If we restrict ourselves to one spatial dimension, we prove the existence of weak solution to the problem where the flux has merely monotone jumps; in such a setting we do not require any continuity of the flux at zero.
HIGH ENERGY p–p COLLISIONS
Authors: SIDHARTH B. G.
Published: November 2010

We consider p–p collisions at very high energy. This becomes relevant in view of the LHC which has just resumed operation. Such collisions will take place in it and indeed already have taken place. Though recent results at the Tevatron in the U.S. seem to rule out the Higgs bosons, there are other results which are eagerly expected, some of these are surveyed here.
COMBINED EFFECTS OF SELECTIVE PHOTOTHERMAL THERAPY AND IMMUNOADJUVANT AGAINST STAGE IV BREAST CANCER
Authors: LI XIAOSONG , HODE TOMAS , GUERRA MARIA C. , FERREL GABRIELA L. , LUNN JOHN A. , ADALSTEINSSON ORN , NORDQUIST ROBERT E. , CHEN WEI R.
Published: November 2010

Metastasis to distant sites is a severe treatment challenge and a major cause of death for breast cancer patients. Laser immunotherapy (LIT) is a novel technique, combining a selective photothermal therapy with local application of glycated chitosan, a potent immunoadjuvant. The pre-clinical studies of LIT have shown its unique characteristics in generating specific antitumor immunity. The clinical application of LIT in the treatment of melanoma patients has achieved preliminary success. Recently, LIT has been used to treat late-stage breast cancer patients. Here we report for the first time the clinical results of this combination therapy in breast cancer patients. The LIT treatment procedures are presented and the medical history of two stage IV breast cancer patients is reviewed. Most of the breast cancer lesions and the metastasis of lung and brain disappeared after repeated treatments of LIT. One patient achieved complete response; the other achieved partial response at the time of this report. Although there is still a long way for LIT to become a standard modality for breast cancer treatment, the results of this study indicated its promising future.
A counterexample-guided abstraction-refinement framework for markov decision processes
Authors: Chadha Rohit , Viswanathan Mahesh
Published: November 2010

The main challenge in using abstractions effectively is to construct a suitable abstraction for the system being verified. One approach that tries to address this problem is that of
counterexample guided abstraction refinement (CEGAR)
, wherein one starts with a coarse abstraction of the system, and progressively refines it, based on invalid counterexamples seen in prior model checking runs, until either an abstraction proves the correctness of the system or a valid counterexample is generated. While CEGAR has been successfully used in verifying nonprobabilistic systems automatically, CEGAR has only recently been investigated in the context of probabilistic systems. The main issues that need to be tackled in order to extend the approach to probabilistic systems is a suitable notion of “counterexample”, algorithms to generate counterexamples, check their validity, and then automatically refine an abstraction based on an invalid counterexample. In this article, we address these issues, and present a CEGAR framework for Markov decision processes.
An inclusion theorem for defeasible logics
Authors: Billington David , Antoniou Grigoris , Governatori Guido , Maher Michael
Published: November 2010

Defeasible reasoning is a computationally simple nonmonotonic reasoning approach that has attracted significant theoretical and practical attention. It comprises a family of logics that capture different intuitions, among them ambiguity propagation versus ambiguity blocking, and the adoption or rejection of team defeat. This article provides a compact presentation of the defeasible logic variants, and derives an inclusion theorem which shows that different notions of provability in defeasible logic form a chain of levels of proof.
Random variate generation by numerical inversion when only the density is known
Authors: Derflinger Gerhard , Hörmann Wolfgang , Leydold Josef
Published: November 2010

We present a numerical inversion method for generating random variates from continuous distributions when only the density function is given. The algorithm is based on polynomial interpolation of the inverse CDF and Gauss-Lobatto integration. The user can select the required precision, which may be close to machine precision for smooth, bounded densities; the necessary tables have moderate size. Our computational experiments with the classical standard distributions (normal, beta, gamma, t-distributions) and with the noncentral chi-square, hyperbolic, generalized hyperbolic, and stable distributions showed that our algorithm always reaches the required precision. The setup time is moderate and the marginal execution time is very fast and nearly the same for all distributions. Thus for the case that large samples with fixed parameters are required the proposed algorithm is the fastest inversion method known. Speed-up factors up to 1000 are obtained when compared to inversion algorithms developed for the specific distributions. This makes our algorithm especially attractive for the simulation of copulas and for quasi--Monte Carlo applications.
Crowd modeling and simulation technologies
Authors: Zhou Suiping , Chen Dan , Cai Wentong , Luo Linbo , Low Malcolm Yoke Hean , Tian Feng , Tay Victor Su-Han , Ong Darren Wee Sze , Hamilton Benjamin D.
Published: November 2010

As a collective and highly dynamic social group, the human crowd is a fascinating phenomenon that has been frequently studied by experts from various areas. Recently, computer-based modeling and simulation technologies have emerged to support investigation of the dynamics of crowds, such as a crowd's behaviors under normal and emergent situations. This article assesses the major existing technologies for crowd modeling and simulation. We first propose a two-dimensional categorization mechanism to classify existing work depending on the
size
of crowds and the
time-scale
of the crowd phenomena of interest. Four evaluation criteria have also been introduced to evaluate existing crowd simulation systems from the point of view of both a modeler and an end-user.

We have discussed some influential existing work in crowd modeling and simulation regarding their major features, performance as well as the technologies used in this work. We have also discussed some open problems in the area. This article will provide the researchers with useful information and insights on the state of the art of the technologies in crowd modeling and simulation as well as future research directions.
ℓ
1
-Sparse reconstruction of sharp point set surfaces
Authors: Avron Haim , Sharf Andrei , Greif Chen , Cohen-Or Daniel
Published: November 2010

We introduce an ℓ
1
-sparse method for the reconstruction of a piecewise smooth point set surface. The technique is motivated by recent advancements in sparse signal reconstruction. The assumption underlying our work is that common objects, even geometrically complex ones, can typically be characterized by a rather small number of features. This, in turn, naturally lends itself to incorporating the powerful notion of sparsity into the model. The sparse reconstruction principle gives rise to a reconstructed point set surface that consists mainly of smooth modes, with the residual of the objective function strongly concentrated near sharp features. Our technique is capable of recovering orientation and positions of highly noisy point sets. The global nature of the optimization yields a sparse solution and avoids local minima. Using an interior-point log-barrier solver with a customized preconditioning scheme, the solver for the corresponding convex optimization problem is competitive and the results are of high quality.
The Art of Medaka Genetics and Genomics: What Makes Them So Unique?
Authors: Takeda Hiroyuki , Shimada Atsuko
Published: November 2010

The medaka fish, Oryzias latipes, is an emerging vertebrate model and now has a high quality draft genome and a number of unique mutants. The long history of medaka research in Japan has provided medaka with unique features, which are complementary to other vertebrate models. A large collection of spontaneous mutants collected over a century, the presence of highly polymorphic inbred lines established over decades, and the recently completed genome sequence all give the medaka a big boost. This review focuses on the state of the art in medaka genetics and genomics, such as the first isolation of active transposons in vertebrates, the influence of chromatin structure on sequence variation, fine quantitative trait locus (QTL) analysis, and versatile mutants as human disease models.
Variable Tandem Repeats Accelerate Evolution of Coding and Regulatory Sequences
Authors: Gemayel Rita , Vinces Marcelo D. , Legendre Matthieu , Verstrepen Kevin J.
Published: November 2010

Genotype-to-phenotype mapping commonly focuses on two major classes of mutations: single nucleotide polymorphisms (SNPs) and copy number variation (CNV). Here, we discuss an underestimated third class of genotypic variation: changes in microsatellite and minisatellite repeats. Such tandem repeats (TRs) are ubiquitous, unstable genomic elements that have historically been designated as nonfunctional “junk DNA” and are therefore mostly ignored in comparative genomics. However, as many as 10% to 20% of eukaryotic genes and promoters contain an unstable repeat tract. Mutations in these repeats often have fascinating phenotypic consequences. For example, changes in unstable repeats located in or near human genes can lead to neurodegenerative diseases such as Huntington disease. Apart from their role in disease, variable repeats also confer useful phenotypic variability, including cell surface variability, plasticity in skeletal morphology, and tuning of the circadian rhythm. As such, TRs combine characteristics of genetic and epigenetic changes that may facilitate organismal evolvability.
Circadian Control of Global Gene Expression Patterns
Authors: Doherty Colleen J. , Kay Steve A.
Published: November 2010

An internal time-keeping mechanism has been observed in almost every organism studied from archaea to humans. This circadian clock provides a competitive advantage in fitness and survival ( 18 , 30 , 95 , 129 , 137 ). Researchers have uncovered the molecular composition of this internal clock by combining enzymology, molecular biology, genetics, and modeling approaches. However, understanding the mechanistic link between the clock and output responses has been elusive. In three model organisms, Arabidopsis thaliana, Drosophila melanogaster, and Mus musculus, whole-genome expression arrays have enabled researchers to investigate how maintaining a time-keeping mechanism connects to an adaptive advantage. Here, we review the impacts transcriptomics have had on our understanding of the clock and how this molecular clock connects with system-level circadian responses. We explore the discoveries made possible by high-throughput RNA assays, the network approaches used to investigate these large transcript datasets, and potential future directions.
New Insights into Plant Responses to the Attack from Insect Herbivores
Authors: Wu Jianqiang , Baldwin Ian T.
Published: November 2010

Plants have evolved sophisticated systems to cope with herbivore challenges. When plants perceive herbivore-derived physical and chemical cues, such as elicitors in insects' oral secretions and compounds in oviposition fluids, plants dramatically reshape their transcriptomes, proteomes, and metabolomes. All these herbivory-induced changes are mediated by elaborate signaling networks, which include receptors/ sensors, Ca2+ influxes, kinase cascades, reactive oxygen species, and phytohormone signaling pathways. Furthermore, herbivory induces defense responses not only in the wounded regions but also in undamaged regions in the attacked leaves and in distal intact (systemic) leaves. Here, we review recent progress in understanding plant perception of herbivory and oviposition, and the herbivory-induced early signaling events and their biological functions. We consider the intraspecific phenotypic diversity of plant responses to herbivory and discuss the underlying genetic variation. We also discuss new tools and technical challenges in studying plant-herbivore interactions.
Protein Homeostasis and the Phenotypic Manifestation of Genetic Diversity: Principles and Mechanisms
Authors: Jarosz Daniel F. , Taipale Mikko , Lindquist Susan
Published: November 2010

Changing a single nucleotide in a genome can have profound consequences under some conditions, but the same change can have no consequences under others. Indeed, organisms can be surprisingly robust to environmental and genetic perturbations. Yet, the mechanisms underlying such robustness are controversial. Moreover, how they might affect evolutionary change remains enigmatic. Here, we review the recently appreciated central role of protein homeostasis in buffering and potentiating genetic variation and discuss how these processes mediate the critical influence of the environment on the relationship between genotype and phenotype. Deciphering how robustness emerges from biological organization and the mechanisms by which it is overcome in changing environments will lead to a more complete understanding of both fundamental evolutionary processes and diverse human diseases.
Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat
Authors: Navarro Víctor M. , Castellano Juan M. , McConkey Sarah M. , Pineda Rafael , Ruiz-Pino Francisco , Pinilla Leonor , Clifton Donald K. , Tena-Sempere Manuel , Steiner Robert A.
Published: November 2010

Neurokinin B (NKB) and its cognate receptor neurokinin 3 (NK3R) play a critical role in reproduction. NKB and NK3R are coexpressed with dynorphin ( Dyn) and kisspeptin ( Kiss1) genes in neurons of the arcuate nucleus (Arc). However, the mechanisms of action of NKB as a cotransmitter with kisspeptin and dynorphin remain poorly understood. We explored the role of NKB in the control of LH secretion in the female rat as follows. 1) We examined the effect of an NKB agonist (senktide, 600 pmol, administered into the lateral cerebral ventricle) on luteinizing hormone (LH) secretion. In the presence of physiological levels of estradiol (E2), senktide induced a profound increase in serum levels of LH and a 10-fold increase in the number of Kiss1 neurons expressing c -fos in the Arc ( P < 0.01 for both). 2) We mapped the distribution of NKB and NK3R mRNAs in the central forebrain and found that both are widely expressed, with intense expression in several hypothalamic nuclei that control reproduction, including the Arc. 3) We studied the effect of E2 on the expression of NKB and NK3R mRNAs in the Arc and found that E2 inhibits the expression of both genes ( P < 0.01) and that the expression of NKB and NK3R reaches its nadir on the afternoon of proestrus (when circulating levels of E2 are high). These observations suggest that NKB/NK3R signaling in Kiss1/NKB/Dyn-producing neurons in the Arc has a pivotal role in the control of gonadotropin-releasing hormone (GnRH)/LH secretion and its regulation by E2-dependent negative feedback in the rat.
Silencing Kinase-Interacting Stathmin Gene Enhances Erlotinib Sensitivity by Inhibiting Ser10 p27 Phosphorylation in Epidermal Growth Factor Receptor–Expressing Breast Cancer
Authors: Zhang Dongwei , Tari Ana M. , Akar Ugur , Arun Banu K. , LaFortune Tiffany A. , Nieves-Alicea Rene , Hortobagyi Gabriel N. , Ueno Naoto T.
Published: November 2010

The epidermal growth factor receptor (EGFR) signaling pathway has emerged as a promising target for cancer therapy. EGFR tyrosine kinase inhibitors (TKI) such as erlotinib have been approved for cancer treatment but have shown very limited activity in breast cancer patients. Clarifying the molecular mechanism underlying resistance to EGFR TKIs could lead to more effective treatment against breast cancer. We previously reported that the sensitivity of breast cancer cells to erlotinib is partially dependent on p27 and that cytoplasmic localization of p27 is associated with erlotinib resistance. In the present study, we found that erlotinib induces p27 phosphorylation at Ser10 (S10), and S10 p27 phosphorylation leads to erlotinib resistance in EGFR-expressing breast cancer. Inhibiting S10 phosphorylation of p27 by knocking down human kinase-interacting stathmin (KIS), a nuclear protein that can phosphorylate p27 at S10, led to p27 accumulation in the nucleus and enhanced erlotinib-mediated cytotoxicity. Further, in vivo KIS gene silencing enhanced the antitumor activity of erlotinib in an orthotopic breast cancer xenograft model. KIS depletion also enhanced erlotinib sensitivity in erlotinib-resistant EGFR-expressing triple-negative breast cancer cells. Our study provides a rationale for the development of combinations of erlotinib with KIS inhibition to overcome EGFR TKI resistance in EGFR-expressing breast cancer. Mol Cancer Ther; 9(11); 3090–9. ©2010 AACR.
Exon 7 Deletion in the bcr-abl Gene Is Frequent in Chronic Myeloid Leukemia Patients and Is Not Correlated with Resistance against Imatinib
Authors: Gaillard Jean-Baptiste , Arnould Cécile , Bravo Sophie , Donadio Daniel , Exbrayat Carole , Jourdan Eric , Reboul Dorothée , Chiesa Jean , Lavabre-Bertrand Thierry
Published: November 2010

Chronic myeloid leukemia (CML) patients treated with imatinib develop frequent resistance generally due to a point mutation. Recently, large rearrangements of abl sequence have also been described. In this study, we focused on the complete deletion of exon 7. We screened for bcr-abldelexon7 in 63 resistant patients by high-resolution melting (HRM) analysis and direct sequencing. Moreover, we analyzed expression of abldelexon7 and bcr-abldelexon7 in 17 CML patients at diagnosis, 32 patients at resistance, and 20 negative controls by quantitative PCR or fragment length analysis. bcr-abldelexon7 was detected on 34 (54%) among 63 resistant patients by HRM, showing an increase in the sensitivity of screening, because only 3.2% could be detected by direct sequencing. This deletion was not associated with a point mutation (P = 0.3362). In addition, abldelexon7 was found in all tested samples with the same pattern of expression, suggesting an alternative splicing mechanism. In the bcr-abl component, there was no statistical difference between CML patients at diagnosis and resistant patients (P = 0.2815) as regarding bcr-abldelexon7 proportion, thus arguing against involvement of deletion in resistance. Moreover, among two patients harboring bcr-abldelexon7 at diagnosis, one experienced a complete disappearance of this transcript, and the other decreased >75% at resistance. In conclusion, bcr-abldelexon7 is frequently observed in CML patients when using sensitive techniques. It seems to be the result of an alternative splicing mechanism and to be independent from the occurrence of resistance. Mol Cancer Ther; 9(11); 3083–9. ©2010 AACR.
HOXC8 Inhibits Androgen Receptor Signaling in Human Prostate Cancer Cells by Inhibiting SRC-3 Recruitment to Direct Androgen Target Genes
Authors: Axlund Sunshine Daddario , Lambert James R. , Nordeen Steven K.
Published: November 2010

HOX (homeobox) genes encode homeodomain-containing transcription factors critical to development, differentiation, and homeostasis. Their dysregulation has been implicated in a variety of cancers. Previously, we showed that a subset of genes of the HOXC cluster is upregulated in primary prostate tumors, lymph node metastases, and malignant prostate cell lines. In the present study, we show that HOXC8 inhibits androgen receptor (AR)-mediated gene induction in LNCaP prostate cancer cells and HPr-1 AR, a nontumorigenic prostate epithelial cell line. Mechanistically, HOXC8 blocks the AR-dependent recruitment of the steroid receptor coactivators steroid receptor coactivator-3 (SRC-3), and CREB binding protein to the androgen-regulated prostate-specific antigen gene enhancer and inhibits histone acetylation of androgen-regulated genes. Inhibition of androgen induction by HOXC8 is reversed upon expression of SRC-3, a member of the SRC/p160 steroid receptor cofactor family. Coimmunoprecipitation studies show that HOXC8 expression inhibits the hormone-dependent interaction of AR and SRC-3. Finally, HOXC8 expression increases invasion in HPr-1 AR nontumorigenic cells. These data suggest a complex role for HOXC8 in prostate cancer, promoting invasiveness while inhibiting AR-mediated gene induction at androgen response element–regulated genes associated with differentiated function of the prostate. A greater understanding of HOXC8 actions in the prostate and its interactions with androgen signaling pathways may elucidate mechanisms driving the onset and progression of prostate cancer. Mol Cancer Res; 8(12); 1643–55. ©2010 AACR.
Black Raspberries Inhibit Intestinal Tumorigenesis in Apc1638+/− and Muc2−/− Mouse Models of Colorectal Cancer
Authors: Bi Xiuli , Fang Wenfeng , Wang Li-Shu , Stoner Gary D. , Yang Wancai
Published: November 2010

Freeze-dried black raspberries (BRB) produce chemopreventive effects in a rat model of colon carcinogenesis; however, the mechanisms of inhibition were not determined. Herein, we used two mouse models of human colorectal cancer to determine if dietary BRBs would inhibit colorectal tumor development and to investigate the underlying mechanisms. We found that a 12-week feeding of BRBs significantly inhibited intestinal tumor formation in both models; reducing tumor incidence by 45% and tumor multiplicity by 60% in Apc1638+/− mice and tumor incidence and multiplicity by 50% in Muc2−/− mice. Mechanistic studies revealed that BRBs inhibit tumor development in Apc1638+/− mice by suppressing β-catenin signaling and in Muc2−/− mice by reducing chronic inflammation. Intestinal cell proliferation was inhibited by BRBs in both animal models; however, the extent of mucus cell differentiation was not changed in either model. Collectively, our data suggest that BRBs are highly effective in preventing intestinal tumor development in both Apc1638+/− and Muc2−/− mice through targeting multiple signaling pathways. Cancer Prev Res; 3(11); 1443–50. ©2010 AACR.
Increased Risk of Serious Hemorrhage with Bevacizumab in Cancer Patients: A Meta-Analysis
Authors: Hapani Sanjaykumar , Sher Amna , Chu David , Wu Shenhong
Published: November 2010

Background: The role of the widely-used angiogenesis inhibitor bevacizumab in the development of serious hemorrhage is not well defined in cancer patients. This study was conducted to determine the overall risk of hemorrhage with bevacizumab by a systematic review and meta-analysis of randomized controlled trials (RCT). Methods: Databases from PubMed and the Web of Science from January 1966 to May 2009 and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences from January 2000 to May 2009 were searched to identify relevant studies. Eligible studies included prospective RCTs in which bevacizumab was compared to controls concurrently with antineoplastic therapy. Summary incidence rates, relative risks (RR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models. Results: A total of 12,617 patients with a variety of solid tumors from 20 RCTs were included for analysis. The incidence of all-grade hemorrhage was 30.4% (95% CI 21.5–40.9), with 3.5% (95% CI 2.2–5.7%) being high grade (grade 3–5). Overall, bevacizumab significantly increased the risk of bleeding with an RR of 2.48 (95% CI 1.93–3.18) when compared to the controls, with RRs of 3.02 (95% CI 2.42–3.78) and 2.01 (95% CI 1.43–2.83) at 5 and 2.5 mg/kg/week, respectively. Significantly increased risks for epistaxis or pulmonary hemorrhage were observed. In addition, bevacizumab significantly increased the risk of high-grade bleeding with an RR of 1.91 (95% CI 1.36–2.68). The risk of fatal bleeding was low (0.8%; 95% CI 0.4–1.7), and significantly elevated only in lung cancer (RR 5.02; 95% CI 1.52–16.66). Conclusion: Bevacizumab may significantly increase the risk of serious hemorrhage in cancer patients.
Trimodal Therapy for Inflammatory Breast Cancer: A Surgeon’s Perspective
Authors: Li Benjamin D. , Sicard Mark A. , Ampil Fred , Abreo Fleurette , Lilien David , Chu Quyen D. , Burton Gary V.
Published: November 2010

Inflammatory breast cancer (IBC) is a rare and most aggressive form of breast cancer. The onset and progression of disease are rapid; diagnosis must be made expediently to initiate treatment quickly. In this review, the clinical presentation, trimodal therapy, surgical principles and a brief summary of the Louisiana State University at Shreveport experience with IBC are presented. With this aggressive approach, 5-year survival of better than 40–50% can be expected. This represents a substantive improvement in clinical outcome for IBC patients compared with 30 years ago.
Level of Heat Shock Proteins Decreases in Individuals Carrying B-Chromosomes in the Grasshopper Eyprepocnemis plorans
Authors: Teruel M. , Sørensen J.G. , Loeschcke V. , Cabrero J. , Perfectti F. , Camacho J.P.M.
Published: November 2010

We analyzed the effect of B-chromosome presence on expression level of heat shock protein 70 (Hsp70) in cerebral ganglion and gonad in both males and females of the grasshopper Eyprepocnemis plorans. Two natural Spanish populations, Salobreña (Granada) and Torrox (Málaga) were assayed, the former harbouring a neutralized (non-driving) B-chromosome (B2) and the latter a parasitic (driving) B-chromosome (B24). The analysis was performed by Western blotting, immunostaining and densitometric measuring expression level of the Hsp70 family in adult individuals. The results showed that Hsp70 levels of testis were significantly higher in Salobreña than Torrox, and were significantly lower in testes of B-carrying males from both populations. A similar effect was observed in the ovary of females from Torrox. No effect was, however, observed in cerebral ganglia in any sex or population. B-chromosome effects in Torrox showed a dose-dependent pattern. The results point to an interesting interaction between B-chromosome and stress protein expression in reproductive tissue.
Involvement of Dystroglycan in Epithelial-Mesenchymal Transition during Chick Gastrulation
Authors: Nakaya Yukiko , Sukowati Erike W. , Alev Cantas , Nakazawa Fumie , Sheng Guojun
Published: November 2010

Regulated disruption of the basement membrane (BM) is a critical step in many epithelial-mesenchymal transition (EMT) processes. Molecular mechanisms controlling the interaction between the BM and the basal membrane of epithelial cells and its subsequent disruption during EMT are poorly understood. Using chick embryos as a model, we analyzed the molecular complexity of this interaction during gastrulation EMT. Transcriptome data indicated that the BM of the gastrulation stage chick epiblast contains a full range of BM component proteins with unique subtype combinations. Integrins and dystroglycan are 2 major groups of basal membrane proteins involved in BM interaction. We provide evidence that dystroglycan gene expression is restricted to the epiblast during early development and its expression is downregulated in cells undergoing gastrulation EMT. The β-dystroglycan protein is localized to the basolateral membrane in epiblast cells and the basal localization is lost in cells undergoing EMT. Disruption of actin filaments leads to a decrease in the lateral membrane localization of β-dystroglycan and a relative increase in basal membrane localization, whereas disruption of microtubules leads to the loss of BM/basal membrane interaction and basal membrane β-dystroglycan localization. Overall, these data suggest an involvement of dystroglycan, especially the regulation of its expression and localization, in gastrulation EMT.
Defining the E-Cadherin Repressor Interactome in Epithelial-Mesenchymal Transition: The PMC42 Model as a Case Study
Authors: Hugo Honor J. , Kokkinos Maria I. , Blick Tony , Ackland M. Leigh , Thompson Erik W. , Newgreen Donald F.
Published: November 2010

Epithelial-mesenchymal transition (EMT) is a feature of migratory cellular processes in all stages of life, including embryonic development and wound healing. Importantly, EMT features cluster with disease states such as chronic fibrosis and cancer. The dissolution of the E-cadherin-mediated adherens junction (AJ) is a key preliminary step in EMT and may occur early or late in the growing epithelial tumour. This is a first step for tumour cells towards stromal invasion, intravasation, extravasation and distant metastasis. The AJ may be inactivated in EMT by directed E-cadherin cleavage; however, it is increasingly evident that the majority of AJ changes are transcriptional and mediated by an expanding group of transcription factors acting directly or indirectly to repress E-cadherin expression. A review of the current literature has revealed that these factors may regulate each other in a hierarchical pattern where Snail1 (formerly Snail) and Snail2 (formerly Slug) are initially induced, leading to the activation of Zeb family members, TCF3, TCF4, Twist, Goosecoid and FOXC2. Within this general pathway, many inter-regulatory relationships have been defined which may be important in maintaining the EMT phenotype. This may be important given the short half-life of Snail1 protein. We have investigated these inter-regulatory relationships in the mesenchymal breast carcinoma cell line PMC42 (also known as PMC42ET) and its epithelial derivative, PMC42LA. This review also discusses several newly described regulators of E-cadherin repressors including oestrogen receptor-α and new discoveries in hypoxia- and growth factor-induced EMT. Finally, we evaluated how these findings may influence approaches to current cancer treatment.
Characterization and Genomic Organization of PERI, a Repetitive DNA in the Drosophila buzzatii Cluster Related to DINE-1 Transposable Elements and Highly Abundant in the Sex Chromosomes
Authors: Kuhn G.C.S. , Heslop-Harrison J.S.
Published: November 2010

Background/Aims: Transposable elements (TEs) are dynamic components of eukaryotic genomes. We aimed to characterize TEs to help elucidate their impact on the genomic architecture, diversity and evolution of chromosomes in the D. buzzatii cluster of species (repleta group). Methods: A full TE element of D. buzzatii, named PERI, was identified in a BAC clone available in GenBank. PERI was further analysed using bioinformatics tools, PCR and in-situ hybridization to metaphase chromosomes and DNA fibers. Results: PERI shares several structures in common with DINE-1, an abundant TE found widespread along the Drosophila genus. The central region of PERI is very dynamic but revealed a disrupted pattern of nucleotide variability among its internal tandem repeats. The minimal sequence variation in D. serido suggests recent amplification. PERI accumulates near or at heterochromatic regions of all 6 pairs of chromosomes, especially on the sex chromosomes, with some clustering. Conclusions: PERI is an abundant type of DINE-1 transposon but with characteristic sequence signatures and probably restricted to the buzzatii complex. The conservation of different central domains and association with genes suggests selective constraints. Although at or near heterochromatin, the distribution of PERI does not overlap with satDNAs, probably a consequence of functional or molecular constraints.
Lichen Planus Occurring after Influenza Vaccination: Report of Three Cases and Review of the Literature
Authors: Sato Noriko Aota , Kano Yoko , Shiohara Tetsuo
Published: November 2010

Although influenza vaccine is thought to be effective and safe, it occasionally causes systemic reactions such as toxic epidermal necrolysis, bullous pemphigoid, lichen planus (LP), etc. The period of increased risk of developing these events was different depending on the immune responses induced by the vaccination. We report 3 cases of LP which appeared after an influenza vaccination. Our cases indicate that the period of increased risk of developing vaccine-related LP was concentrated within 2 weeks after vaccination, and that the vaccine alone represents a triggering factor necessary for immune alteration sufficient for the development of LP. Because these adverse events tend to develop over a predictable time course, the time of onset may give an important clue to the diagnosis of vaccine-related diseases. We suggest that a history of recent vaccination should be sought in all patients presenting with linear LP.
Induction of B Cell-Activating Factor by Viral Infection Is a General Phenomenon, but the Types of Viruses and Mechanisms Depend on Cell Type
Authors: Ittah Marc , Miceli-Richard Corinne , Lebon Pierre , Pallier Coralie , Lepajolec Christine , Mariette Xavier
Published: November 2010

B cell-activating factor of the TNF family (BAFF) plays a key role in promoting B lymphocyte activation and survival. We previously showed in primary Sjögren’s syndrome that salivary gland epithelial cells (SGECs), the resident targeted cells of autoimmunity in this disease, can produce BAFF after infection with a double-stranded RNA (dsRNA) virus by a protein kinase RNA (PKR)-dependent mechanism. This study aimed to assess the effect of different viruses on various cell types – SGECs but also dendritic cells (DCs) and monocytes – in the induction of BAFF. BAFF induction was observed after Sendai virus infection of monocytes and SGECs, as well as poly(I:C) stimulation of DCs. However, PKR inhibition by 2-aminopurine failed to reduce BAFF expression in these infected or stimulated cells. Conversely, in Sendai virus-infected monocytes, blocking type 1 interferon (IFN) receptor by anti-IFNAR1 antibody strongly inhibited BAFF expression. These results provide additional data suggesting that both dsRNA virus stimulation of DCs and single-stranded RNA virus infection of SGECs or monocytes can induce BAFF expression, but through a PKR-independent mechanism for these 3 cell types and a type 1 IFN-dependent mechanism in monocytes and SGECs. Thus, BAFF induction by viral infection is a general phenomenon, but the types of viruses and mechanisms of the induction depend on the cell type.
Coagulation Systems of Invertebrates and Vertebrates and Their Roles in Innate Immunity: The Same Side of Two Coins?
Authors: Loof Torsten G. , Schmidt Otto , Herwald Heiko , Theopold Ulrich
Published: November 2010

Bacterial infections represent a serious health care problem, and all multicellular organisms have developed defense mechanisms to eliminate pathogens that enter the host via different paths including wounds. Many invertebrates have an open circulatory system, and effective coagulation systems are in place to ensure fast and efficient closure of wounds. It was proposed early on that coagulation systems in invertebrates play a major role not only in sealing wounds but also in preventing systemic infections. More recent evidence suggests that vertebrates, too, rely on clotting as an immune effector mechanism. Here we discuss the evolution of clotting systems against the background of their versatile function in innate immunity.
Description of Ruehmaphelenchus thailandae n. sp. (Nematoda: Aphelenchoididae) found in dunnage from Thailand
Authors: Gu Jianfeng , Wang Jiangling
Published: November 2010

Ruehmaphelenchus thailandae n. sp., isolated from deciduous dunnage from Thailand, is described and figured. The new species is characterised by the relatively stout body (a = 28.6 and 27.6 for males and females, respectively), three lines in the lateral field, spicules relatively small (12.0-13.3 μm) with weakly developed condylus and rostrum, bursa absent, vulva located at 79.5% of body length, vulval lips slightly swollen, length of post-uterine branch more than half of vulva to anus distance, female tail conoid, ca two anal body diam. long and with a broad terminal process up to 12 μm long. The new species is the third known for the genus. It can be distinguished from R. martinii and R. asiaticus mainly by the different shape and size of its spicules and different shape of the female tail terminus. The separate species status is also supported by ITS-RFLP pattern. Additional measurements of paratype R. asiaticus are appended.
One Market, Two Courts: Legal Pluralism vs. Homogeneity in the European Economic Area
Authors: Fredriksen Halvard Haukeland
Published: November 2010

In this article the apparent incompatibility between the judicial architecture of the European Economic Area (EEA) and the overall goal of uniform interpretation and application of the common rules in all EEA States is examined. In practice, homogeneity appears achievable only if the European Free Trade Association (EFTA) Court succumbs to the European Court of Justice (ECJ), granting the latter the final word on the interpretation of the EEA Agreement. It is argued that, as far as substantive EEA law is concerned, this is exactly what the EFTA Court has done over the past 17 years of the EEA's existence. The result is a well-functioning EEA Agreement. The price to pay for the EFTA States is the revelation of the perhaps inconvenient truth that the de facto supreme authority on the interpretation of EEA law rests with the ECJ.