bluuebunny/crossref_metadata_2025_split huggingface dataset:
Equine Infectious Anemia Virus Resists the Antiretroviral Activity of Equine APOBEC3 Proteins through a Packaging-Independent Mechanism
Authors: Bogerd Hal P. , Tallmadge Rebecca L. , Oaks J. Lindsay , Carpenter Susan , Cullen Bryan R. 
Published: September 2008

ABSTRACT

Equine infectious anemia virus (EIAV), uniquely among lentiviruses, does not encode a
vif
gene product. Other lentiviruses, including human immunodeficiency virus type 1 (HIV-1), use Vif to neutralize members of the APOBEC3 (A3) family of intrinsic immunity factors that would otherwise inhibit viral infectivity. This suggests either that equine cells infected by EIAV in vivo do not express active A3 proteins or that EIAV has developed a novel mechanism to avoid inhibition by equine A3 (eA3). Here, we demonstrate that horses encode six distinct A3 proteins, four of which contain a single copy of the cytidine deaminase (CDA) consensus active site and two of which contain two CDA motifs. This represents a level of complexity previously seen only in primates. Phylogenetic analysis of equine single-CDA A3 proteins revealed two proteins related to human A3A (hA3A), one related to hA3C, and one related to hA3H. Both equine double-CDA proteins are similar to hA3F and were named eA3F1 and eA3F2. Analysis of eA3F1 and eA3F2 expression in vivo shows that the mRNAs encoding these proteins are widely expressed, including in cells that are natural EIAV targets. Both eA3F1 and eA3F2 inhibit retrotransposon mobility, while eA3F1 is a potent inhibitor of a Vif-deficient HIV-1 mutant and induces extensive editing of HIV-1 reverse transcripts. However, both eA3F1 and eA3F2 are weak inhibitors of EIAV. Surprisingly, eA3F1 and eA3F2 were packaged into EIAV and HIV-1 virions as effectively as hA3G, although only the latter inhibited EIAV infectivity. Moreover, all three proteins bound both the HIV-1 and EIAV nucleocapsid protein specifically in vitro. It therefore appears that EIAV has evolved a novel mechanism to specifically neutralize the biological activities of the cognate eA3F1 and eA3F2 proteins at a step subsequent to virion incorporation.
Systematic Assembly of a Full-Length Infectious Clone of Human Coronavirus NL63
Authors: Donaldson Eric F. , Yount Boyd , Sims Amy C. , Burkett Susan , Pickles Raymond J. , Baric Ralph S. 
Published: September 2008

ABSTRACT
Historically, coronaviruses were predominantly associated with mild upper respiratory disease in humans. More recently, three novel coronaviruses associated with severe human respiratory disease were found, including (i) the severe acute respiratory syndrome coronavirus, associated with a significant atypical pneumonia and 10% mortality; (ii) HKU-1, associated with chronic pulmonary disease; and (iii) NL63, associated with both upper and lower respiratory tract disease in children and adults worldwide. These discoveries establish coronaviruses as important human pathogens and underscore the need for continued research toward the development of platforms that will enable genetic manipulation of the viral genome, allowing for rapid and rational development and testing of candidate vaccines, vaccine vectors, and therapeutics. In this report, we describe a reverse genetics system for NL63, whereby five contiguous cDNAs that span the entire genome were used to generate a full-length cDNA. Recombinant NL63 viruses which contained the expected marker mutations replicated as efficiently as the wild-type NL63 virus. In addition, we engineered the heterologous green fluorescent protein gene in place of open reading frame 3 (ORF3) of the NL63 clone, simultaneously creating a unique marker for NL63 infection and demonstrating that the ORF3 protein product is nonessential for the replication of NL63 in cell culture. The availability of the NL63 and NL63gfp clones and recombinant viruses provides powerful tools that will help advance our understanding of this important human pathogen.
Morphological quality and nucleic acid preservation in cytopathology
Authors: Gazziero A , Guzzardo V , Aldighieri E , Fassina A 
Published: September 2008

Background:Fixation is a chemical or physical procedure to prevent the degradation of proteins and tissue morphology. To optimise molecular analysis of archival tissues, it is essential that fixation preserves morphology along with protein epitopes and DNA/RNA integrity.Methods:A new formalin-free alcoholic-based fixative, FineFIX, was used to fix 15 serous effusions and 38 fine-needle aspirates, and cellular morphology and nucleic acid quality were evaluated.Results:The cytomorphology of the effusions and fine-needle aspirates obtained with FineFIX fixation was similar to that obtained with formalin-fixed counterparts. Immunocytochemistry showed comparable results with the traditional fixative, but FineFIX preserved higher-molecular-mass DNA and RNA, as demonstrated by successful PCR of large amplification products of >2000 bp.Conclusions:The formalin-free fixative produced not only satisfactory results for immunocytochemistry on cytological smears and cell blocks, but also excellent preservation of DNA and RNA, which can also be efficiently used for sophisticated molecular techniques.
The gross appearances of fine needle aspiration cytology samples: Figure 1
Authors: Mayall F G , Cormack A , McAnulty K , Darlington A 
Published: September 2008

Aims:This study set out to photograph and describe the gross appearances of fine needle aspiration (FNA) cytology samples of commonly encountered lesions.Methods:During a 2 year period, a cytopathologist photographed the gross appearances of near patient FNA samples, concentrating on commonly encountered lesions.Results:The gross appearances are described, accompanied by photographic illustrations.Conclusions:This paper describes and illustrates the gross appearances of FNA cytology samples of some commonly encountered lesions.
2,2-Bis(4-Chlorophenyl)-1,1-Dichloroethylene Stimulates Androgen Independence in Prostate Cancer Cells through Combinatorial Activation of Mutant Androgen Receptor and Mitogen-Activated Protein Kinase Pathways
Authors: Shah Supriya , Hess-Wilson Janet K. , Webb Siobhan , Daly Hannah , Godoy-Tundidor Sonia , Kim Jae , Boldison Joanne , Daaka Yehia , Knudsen Karen E. 
Published: September 2008

AbstractTherapy resistance represents a major clinical challenge in disseminated prostate cancer for which only palliative treatment is available. One phenotype of therapy-resistant tumors is the expression of somatic, gain-of-function mutations of the androgen receptor (AR). Such mutant receptors can use noncanonical endogenous ligands (e.g., estrogen) as agonists, thereby promoting recurrent tumor formation. Additionally, selected AR mutants are sensitized to the estrogenic endocrine-disrupting compound (EDC) bisphenol A, present in the environment. Herein, screening of additional EDCs revealed that multiple tumor-derived AR mutants (including T877A, H874Y, L701H, and V715M) are sensitized to activation by the pesticide 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (DDE), thus indicating that this agent may impinge on AR signaling in cancer cells. Further investigation showed that DDE induced mutant AR recruitment to the prostate-specific antigen regulatory region, concomitant with an enhancement of target gene expression, and androgen-independent proliferation. By contrast, neither AR activation nor altered cellular proliferation was observed in cells expressing wild-type AR. Activation of signal transduction pathways was also observed based on rapid phosphorylation of mitogen-activated protein kinase (MAPK) and vasodilator-stimulated phosphoprotein, although only MAPK activation was associated with DDE-induced cellular proliferation. Functional analyses showed that both mutant AR and MAPK pathways contribute to the proliferative action of DDE, as evidenced through selective abrogation of each pathway. Together, these data show that exposure to environmentally relevant doses of EDCs can promote androgen-independent cellular proliferation in tumor cells expressing mutant AR and that DDE uses both mutant AR and MAPK pathways to exert its mitogenic activity. (Mol Cancer Res 2008;6(9):1507–20)
Up-Regulation of Rho/ROCK Signaling in Sarcoma Cells Drives Invasion and Increased Generation of Protrusive Forces
Authors: Rösel Daniel , Brábek Jan , Tolde Ondřej , Mierke Claudia T. , Zitterbart Daniel P. , Raupach Carina , Bicanová Kristýna , Kollmannsberger Philip , Paňková Daniela , Veselý Pavel , Folk Petr , Fabry Ben 
Published: September 2008

AbstractTumor cell invasion is the most critical step of metastasis. Determination of the mode of invasion within the particular tumor is critical for effective cancer treatment. Protease-independent amoeboid mode of invasion has been described in carcinoma cells and more recently in sarcoma cells on treatment with protease inhibitors. To analyze invasive behavior, we compared highly metastatic sarcoma cells with parental nonmetastatic cells. The metastatic cells exhibited a functional up-regulation of Rho/ROCK signaling and, similarly to carcinoma cells, an amoeboid mode of invasion. Using confocal and traction force microscopy, we showed that an up-regulation of Rho/ROCK signaling leads to increased cytoskeletal dynamics, myosin light chain localization, and increased tractions at the leading edge of the cells and that all of these contributed to increased cell invasiveness in a three-dimensional collagen matrix. We conclude that cells of mesenchymal origin can use the amoeboid nonmesenchymal mode of invasion as their primary invading mechanism and show the dependence of ROCK-mediated amoeboid mode of invasion on the increased capacity of cells to generate force. (Mol Cancer Res 2008;6(9):1410–20)
Sphingosine-1-Phosphate and Interleukin-1 Independently Regulate Plasminogen Activator Inhibitor-1 and Urokinase-Type Plasminogen Activator Receptor Expression in Glioblastoma Cells: Implications for Invasiveness
Authors: Bryan Lauren , Paugh Barbara S. , Kapitonov Dmitri , Wilczynska Katarzyna M. , Alvarez Silvina M. , Singh Sandeep K. , Milstien Sheldon , Spiegel Sarah , Kordula Tomasz 
Published: September 2008

Abstract
Glioblastoma multiforme is an invasive primary brain tumor, which evades the current standard treatments. The invasion of glioblastoma cells into healthy brain tissue partly depends on the proteolytic and nonproteolytic activities of the plasminogen activator system proteins, including the urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1), and a receptor for uPA (uPAR). Here we show that sphingosine-1-phosphate (S1P) and the inflammatory mediator interleukin-1 (IL-1) increase the mRNA and protein expression of PAI-1 and uPAR and enhance the invasion of U373 glioblastoma cells. Although IL-1 enhanced the expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, down-regulation of SphK1 had no effect on the IL-1–induced uPAR or PAI-1 mRNA expression, suggesting that these actions of IL-1 are independent of S1P production. Indeed, the S1P-induced mRNA expression of uPAR and PAI-1 was blocked by the S1P2 receptor antagonist JTE013 and by the down-regulation of S1P2 using siRNA. Accordingly, the inhibition of mitogen-activated protein kinase/extracellular signal–regulated kinase kinase 1/2 and Rho-kinase, two downstream signaling cascades activated by S1P2, blocked the activation of PAI-1 and uPAR mRNA expression by S1P. More importantly, the attachment of glioblastoma cells was inhibited by the addition of exogenous PAI-1 or siRNA to uPAR, whereas the invasion of glioblastoma cells induced by S1P or IL-1 correlated with their ability to enhance the expression of PAI-1 and uPAR. Collectively, these results indicate that S1P and IL-1 activate distinct pathways leading to the mRNA and protein expression of PAI-1 and uPAR, which are important for glioblastoma invasiveness. (Mol Cancer Res 2008;6(9):1469–77)
The Retinoblastoma Protein Tumor Suppressor Is Important for Appropriate Osteoblast Differentiation and Bone Development
Authors: Berman Seth D. , Yuan Tina L. , Miller Emily S. , Lee Eunice Y. , Caron Alicia , Lees Jacqueline A. 
Published: September 2008

Abstract
Mutation of the retinoblastoma (RB) tumor suppressor gene is strongly linked to osteosarcoma formation. This observation and the documented interaction between the retinoblastoma protein (pRb) and Runx2 suggests that pRb is important in bone development. To assess this hypothesis, we used a conditional knockout strategy to generate pRb-deficient embryos that survive to birth. Analysis of these embryos shows that Rb inactivation causes the abnormal development and impaired ossification of several bones, correlating with an impairment in osteoblast differentiation. We further show that Rb inactivation acts to promote osteoblast differentiation in vitro and, through conditional analysis, establish that this occurs in a cell-intrinsic manner. Although these in vivo and in vitro differentiation phenotypes seem paradoxical, we find that Rb-deficient osteoblasts have an impaired ability to exit the cell cycle both in vivo and in vitro that can explain the observed differentiation defects. Consistent with this observation, we show that the cell cycle and the bone defects in Rb-deficient embryos can be suppressed by deletion of E2f1, a known proliferation inducer that acts downstream of Rb. Thus, we conclude that pRb plays a key role in regulating osteoblast differentiation by mediating the inhibition of E2F and consequently promoting cell cycle exit. (Mol Cancer Res 2008;6(9):1440–51)
Notch3 Is a Major Regulator of Vascular Tone in Cerebral and Tail Resistance Arteries
Authors: Belin de Chantemèle E.J. , Retailleau K. , Pinaud F. , Vessières E. , Bocquet A. , Guihot A.L. , Lemaire B. , Domenga V. , Baufreton C. , Loufrani L. , Joutel A. , Henrion D. 
Published: September 2008

Objective—Notch3, a member of the evolutionary conserved Notch receptor family, is primarily expressed in vascular smooth muscle cells. Genetic studies in human and mice revealed a critical role for Notch3 in the structural integrity of distal resistance arteries by regulating arterial differentiation and postnatal maturation.Methods and Results—We investigated the role of Notch3 in vascular tone in small resistance vessels (tail and cerebral arteries) and large (carotid) arteries isolated fromNotch3-deficient mice using arteriography. Passive diameter and compliance were unaltered in mutant arteries. Similarly, contractions to phenylephrine, KCl, angiotensin II, and thromboxane A2 as well as dilation to acetylcholine or sodium nitroprusside were unaffected. However,Notch3deficiency induced a dramatic reduction in pressure-induced myogenic tone associated with a higher flow (shear stress)-mediated dilation in tail and cerebral resistance arteries only. Furthermore, RhoA activity and myosin light chain phosphorylation, measured in pressurized tail arteries, were significantly reduced inNotch3KO mice. Additionally, myogenic tone inhibition by the Rho kinase inhibitor Y27632 was attenuated in mutant tail arteries.Conclusions—Notch3 plays an important role in the control of vascular mechano-transduction, by modulating the RhoA/Rho kinase pathway, with opposite effects on myogenic tone and flow-mediated dilation in the resistance circulation.
Engaging the South: Ming China and Southeast Asia in the Fifteenth Century
Authors: Wade Geoff 
Published: September 2008

AbstractThe fifteenth century witnessed Ming China expanding its interactions with areas to the south—areas which we today refer to as Southeast Asia. This involved overland political expansion, the gradual incorporation of Tai polities, as well as their economic exploitation. The twenty-year incorporation of the Dai Viêt policy was also part of this process. In the maritime realm, following the early fifteenth-century sending of massive armadas in an attempt to achieve a pax Ming in the region, the Ming court made efforts to ban maritime commerce by non-state players. This paper examines the effects that these various Ming policies had on Southeast Asia in the political, economic, technological, and cultural spheres. Le XVIème siècle vit la multiplication des interventions de la Chine des Ming dans la région aujourd'hui dénommée Asie du Sud-Est. Elles entraînèrent une expansion politique terrestre, l'annexion progressive des royaumes Thaïs et leur exploitation économique. L'incorporation du royaume de Dai Viêt à la Chine durant vingt années, s'inscrit dans le même développement. Dans le domaine maritime, le début du XVIème siècle est marqué par l'envoi d'armadas qui tentèrent d'imposer la pax Ming dans l'Asie du Sud-Est., la cour Ming s'efforçant d'exclure le négoce privé du commerce maritime. Cette contribution étudie les effets de l'ensemble des stratégies des Ming en Asie du Sud-Est dans la sphère politique, économique, technologique et culturelle.
The Rise and Fall of the Tujjār Councils of Representatives in Iran, 1884–85
Authors: Gilbar Gad 
Published: September 2008

AbstractIn July 1884 Nāsir al-Dīn Shāh approved the establishment of councils of representatives of the big merchants (majālis-i wukalā-yi tujjār) in the main commercial centers of Iran. Within three to four months, the tujjār elected their councils in eighteen cities and towns in the country. These councils were to supervise commercial activities in Iran, encourage investments in new projects by big local merchants, and above all limit the involvement and interference of both the provincial governors and the local religious leaders in business matters. The establishment of the councils prompted hostility and resistance by both governors and ‘ulamā’ from the very beginning. Events in Tabrīz in November-December 1884 struck a decisive blow to the councils. The institution at that town disbanded in late December, and several weeks later most of the other councils followed suit. In light of these developments, the shah, in February or March 1885, nullified his instructions concerning the establishment of the councils. This article analyzes the conditions and circumstances that prompted the shah and the tujjār to take a step that was without precedent in nineteenth-century Iran or elsewhere in the Middle East. It also studies in detail the events that brought about the end of a promising and significant development. En juillet 1884 Nāsir al-Dīn Shāh approuva l'établissement des conseils représentant les grands marchands (majālis-i wukalā-yi tujjār) dans les principaux centres commerciaux de l'Iran. Ces conseils devaient surveiller les activités commerciales en Iran, encourager les grands marchands locaux à investir dans des projets nouveaux, et tout d'abord restreindre l'influence et les interventions des gouverneurs provinciaux et des autorités religieuses locales dans leurs affaires. Cette initiative provoqua aussitôt l'hostilité et l'opposition des gouverneurs et des ‘Ulamā’.Cette contribution analyse les conditions et les circonstances qui poussèrent le Schah et les tujjār à cette démarche sans précédent dans l'Iran du XIXième siècle et ailleurs dans le Moyen-Orient à cette époque et détaille les événements qui menèrent à l'échec de ce développement prometteur et important.
From Autonomy to Integration? International Law, Free Trade and the Environment
Authors: Mehling Michael , Lindroos Anja 
Published: September 2008

AbstractOur current understanding of so-called “self-contained regimes” is based on an overly simplistic appreciation of how such regimes interact with each other and with the larger body of international law. Drawing on an analysis of WTO case law, this article highlights two distinct normative relations, addressing the relationship of international trade law vis-à-vis general international law and international environmental law. As the analysis reveals, further differentiation of normative relationships is needed to better understand how such seemingly independent regimes operate in a fragmented legal system. It also shows that a recently proposed interpretative tool, systemic integration, raises new questions and challenges traditional conceptions of international treaty law.
Fairness, Promptness and Effectiveness: How the Openness of Good Faith Limits the Flexibility of the DSU
Authors: Panizzon Marion 
Published: September 2008

AbstractThe World Trade Organization Appellate Body has drawn from international legal principles to intensify the normative impact of good faith duties vaguely described in Articles 3(10) and 4(3) of the Dispute Settlement Understanding. In the context of the Appellate Body's repeated rejection of good faith principles in the “substantive” WTO law of the General Agreement on Tariffs and Trade, the General Agreement on Trade in Services and the Agreement on Trade-Related Aspects of Intellectual Property Rights, the development of “procedural” good faith adjudication stands out. Relating procedural good faith adjudication to the level of fairness, the WTO judiciary thus relegates to the past power-oriented, diplomacy-based structures of WTO dispute settlement.This article will show how the general good faith principle served to reduce the flexibility remaining in the WTO's Member-driven dispute settlement procedure, often abused by powerful WTO Members to draw out disputes at the expense of developing country Members. One will also describe how the Appellate Body derived a due process standard, the one of requiring a “fair, prompt and effective” resolution of WTO trade disputes from the good faith obligation in Article 3(10) DSU, while keeping due process distinct from good faith duties.This due process standard enables the Appellate Body to review (and restrict) the use of procedural rights by WTO Members even when the exercise of these rights appears – on its face – consistent with DSU norms.The article finds that the due process standard is a first-time judicial assertion in Appellate Body practice of a broader enforceability of good faith.
Open Method of Coordination: A New Stepping Stone in the Legal Order of International and European Relations
Authors: Haar Beryl ter 
Published: September 2008

AbstractThe open method of coordination is characterised by the combined use of modes of governance and soft law instruments, a combination that is uncommon since they usually are sequentially related to each other: governance leads to soft law. The focus of this paper is therefore on the significance of this combined use for the position of the OMC in the legal order of international and European relations. To determine the OMC's position, the paper first substantiates the soft law aspects of the ideal-type OMC, based on the international relations concept of legalisation, an ideal-type European Community law and the terminology of the gap-thesis. Furthermore, the paper examines the internal and external functioning of the OMC, the latter having focus on, in particular, its relations with Community hard law. The paper concludes by showing that the OMC adds in two ways a new stepping stone into the legal order of international and European relations.