bluuebunny/crossref_metadata_2025_split huggingface dataset:
The O Antigen Enables
Bordetella parapertussis
To Avoid
Bordetella pertussis
-Induced Immunity
Authors: Wolfe Daniel N. , Goebel Elizabeth M. , Bjornstad Ottar N. , Restif Olivier , Harvill Eric T. 
Published: August 2007

ABSTRACT

Bordetella pertussis
and
Bordetella parapertussis
are closely related endemic human pathogens which cause whooping cough, a disease that is reemerging in human populations. Despite how closely related these pathogens are, their coexistence and the limited efficacy of
B. pertussis
vaccines against
B. parapertussis
suggest a lack of cross-protective immunity between the two. We sought to address the ability of infection-induced immunity against one of these pathogens to protect against subsequent infection by the other using a mouse model of infection. Immunity induced by
B. parapertussis
infection protected against subsequent infections by either species. However, immunity induced by
B. pertussis
infection prevented subsequent
B. pertussis
infections but did not protect against
B. parapertussis
infections. The O antigen of
B. parapertussis
inhibited binding of antibodies to the bacterial surface and was required for
B. parapertussis
to colonize mice convalescent from
B. pertussis
infection. Thus, the O antigen of
B. parapertussis
confers asymmetrical cross-immunity between the causative agents of whooping cough. We propose that these findings warrant investigation of the relative role of
B. parapertussis
in the resurgence of whooping cough.
Monomeric Expression of Bovine β2-Integrin Subunits Reveals Their Role inMannheimia haemolyticaLeukotoxin-Induced Biological Effects
Authors: Dassanayake Rohana P. , Maheswaran Samuel K. , Srikumaran Subramaniam 
Published: August 2007

ABSTRACTThe ruminant-specific leukotoxin (Lkt) ofMannheimia haemolyticais the key virulence factor contributing to the pathogenesis of lung injury in bovine pneumonic pasteurellosis. Previous studies by us and others indicate thatM. haemolyticaLkt binds to CD18, the β subunit of bovine β2-integrins on leukocytes, and that the species specificity of Lkt-induced effects is resident in the β subunit CD18 and not in the α subunit CD11. However, Lkt also binds to the CD11a subunit of LFA-1. Furthermore, antibodies specific for CD18 or CD11a inhibit signaling events leading to elevation of intracellular [Ca2+], tyrosine phosphorylation of the cytosolic domain of CD18, and cytolysis of bovine leukocytes. These observations underscore the need for further investigation to identify the precise subunit of bovine LFA-1 utilized byM. haemolyticaLkt as the functional receptor. For this purpose, monomeric bovine CD18 and CD11a and heterodimeric LFA-1 were expressed in the HEK-293 cell line by transfection, and the resulting transfectants were tested for susceptibility to Lkt-induced effects. All three transfectants effectively bound Lkt. However, Lkt-induced cytolysis was observed only with transfectants expressing monomeric bovine CD18 or LFA-1. Furthermore, intracellular [Ca2+] elevation following exposure to Lkt, which is a marker for postbinding signaling leading to cellular activation, was seen only with transfectants expressing monomeric bovine CD18 or LFA-1. These results clearly indicate that the bovine CD18 subunit of β2-integrins is the functional receptor forM. haemolyticaLkt.
Taenia solium
Oncosphere Adhesion to Intestinal Epithelial and Chinese Hamster Ovary Cells In Vitro
Authors: Verastegui Manuela , Gilman Robert H. , Arana Yanina , Barber Dylan , Velásquez Jeanette , Farfán Marilu , Chile Nancy , Kosek Jon C. , Kosek Margaret , Garcia Hector H. , Gonzalez Armando 
Published: August 2007

ABSTRACT

The specific mechanisms underlying
Taenia solium
oncosphere adherence and penetration in the host have not been studied previously. We developed an in vitro adhesion model assay to evaluate the mechanisms of
T. solium
oncosphere adherence to the host cells. The following substrates were used: porcine intestinal mucosal scrapings (PIMS), porcine small intestinal mucosal explants (PSIME), Chinese hamster ovary cells (CHO cells), epithelial cells from ileocecal colorectal adenocarcinoma (HCT-8 cells), and epithelial cells from colorectal adenocarcinoma (Caco-2 cells). CHO cells were used to compare oncosphere adherence to fixed and viable cells, to determine the optimum time of oncosphere incubation, to determine the role of sera and monolayer cell maturation, and to determine the effect of temperature on oncosphere adherence. Light microscopy, scanning microscopy, and transmission microscopy were used to observe morphological characteristics of adhered oncospheres. This study showed in vitro adherence of activated
T. solium
oncospheres to PIMS, PSIME, monolayer CHO cells, Caco-2 cells, and HCT-8 cells. The reproducibility of
T. solium
oncosphere adherence was most easily measured with CHO cells. Adherence was enhanced by serum-binding medium with >5% fetal bovine serum, which resulted in a significantly greater number of oncospheres adhering than the number adhering when serum at a concentration less than 2.5% was used (
P
< 0.05). Oncosphere adherence decreased with incubation of cells at 4°C compared with the adherence at 37°C. Our studies also demonstrated that
T. solium
oncospheres attach to cells with elongated microvillus processes and that the oncospheres expel external secretory vesicles that have the same oncosphere processes.
Stimulated PI3K-AKT Signaling Mediated through Ligand or Radiation-Induced EGFR Depends Indirectly, but not Directly, on Constitutive K-Ras Activity
Authors: Toulany Mahmoud , Baumann Michael , Rodemann H. Peter 
Published: August 2007

AbstractPrevious results showed an inducible radiation sensitivity selectively observable for K-RAS–mutated cell lines as a function of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor blockade of phosphatidylinositol 3-kinase (PI3K)-AKT signaling. Therefore, the role of K-Ras activity for a direct (i.e., through activation of PI3K by K-Ras) or an indirect stimulation of PI3K-AKT signaling (through K-Ras activity–dependent EGFR ligand production) was investigated by means of small interfering RNA and inhibitor approaches as well as ELISA measurements of EGFR ligand production. K-RASmt tumor cells presented a constitutively activated extracellular signal–regulated kinase-1/2 signaling, resulting in enhanced production and secretion of the EGFR ligand amphiregulin (AREG). Medium supernatants conditioned by K-RASmt tumor cells equally efficiently stimulated EGFR signaling into the PI3K-AKT and mitogen-activated protein kinase pathways. Knocking down K-Ras expression by specific small interfering RNA markedly affected autocrine production of AREG, but not PI3K-AKT signaling, after treatment of K-RAS–mutated or wild-type cells with EGFR ligands or exposure to ionizing radiation. These results indicate that PI3K-mediated activation of AKT in K-RASmt human tumor cells as a function of EGFR ligand or radiation stimulus is independent of a direct function of K-Ras enzyme activity but depends on a K-Ras–mediated enhanced production of EGFR ligands (i.e., most likely AREG) through up-regulated extracellular signal–regulated kinase-1/2 signaling. The data provide new differential insight into the importance of K-RAS mutation in the context of PI3K-AKT–mediated radioresistance of EGFR-overexpressing or EGFR-mutated tumors. (Mol Cancer Res 2007;5(8):863–72)
Activated Signal Transducers and Activators of Transcription 3 Signaling Induces CD46 Expression and Protects Human Cancer Cells from Complement-Dependent Cytotoxicity
Authors: Buettner Ralf , Huang Mei , Gritsko Tanya , Karras Jim , Enkemann Steve , Mesa Tania , Nam Sangkil , Yu Hua , Jove Richard 
Published: August 2007

AbstractCD46 is one of the complement-regulatory proteins expressed on the surface of normal and tumor cells for protection against complement-dependent cytotoxicity. Cancer cells need to access the blood circulation for continued growth and metastasis, thus exposing themselves to destruction by complement system components. Previous studies have established that the signal transducers and activators of transcription 3 (STAT3) transcription factor is persistently activated in a wide variety of human cancer cells and primary tumor tissues compared with their normal counterparts. Using microarray gene expression profiling, we identified the CD46 gene as a target for activated STAT3 signaling in human breast and prostate cancer cells. The CD46 promoter contains two binding sites for activated STAT3 and mutations introduced into the major site abolished STAT3 binding. Chromatin immunoprecipitation confirms binding of STAT3 to the CD46 promoter. CD46 promoter activity is induced by activation of STAT3 and blocked by a dominant-negative form of STAT3 in luciferase reporter assays. CD46 mRNA expression is induced by interleukin-6 and by transient transfection of normal human epithelial cells with a persistently active mutant construct of STAT3, STAT3C. Furthermore, we show that inhibition of STAT3-mediated CD46 cell surface expression sensitizes DU145 prostate cancer cells to cytotoxicity in an in vitro complement lysis assay using rabbit anti-DU145 antiserum and rabbit complement. These results show that activated STAT3 signaling induces the CD46 promoter and protects human cancer cells from complement-dependent cytotoxicity, suggesting a potential mechanism whereby oncogenic signaling contributes to tumor cell evasion of antibody-mediated immunity. (Mol Cancer Res 2007;5(8):823–32)
The Opposing Effect of Hypoxia-Inducible Factor-2α on Expression of Telomerase Reverse Transcriptase
Authors: Lou Fenglan , Chen Xinxia , Jalink Marit , Zhu Qingjun , Ge Nan , Zhao Shengtian , Fang Xiaolei , Fan Yidong , Björkholm Magnus , Liu Zhaoxu , Xu Dawei 
Published: August 2007

Abstract
Hypoxia-inducible factor-1α (HIF-1α) has been implicated in the transcriptional regulation of the telomerase reverse transcriptase (hTERT) gene expression and telomerase activity, essential elements for cellular immortalization and transformation. However, controversial results were obtained in different studies. Moreover, it is totally unclear whether HIF-2α, the paralog of HIF-1α, plays a role in regulating hTERT expression. In the present study, we found that hypoxic treatment enhanced hTERT mRNA expression and telomerase activity in three renal cell carcinoma (RCC) cell lines with different genetic backgrounds. Both HIF-1α and HIF-2α were capable of significantly increasing the hTERT promoter activity in these cells. Moreover, depleting HIF-2α led to a down-regulation of hTERT mRNA level in RCC A498 cells expressing constitutive HIF-2α. It was found that HIF-2α bound to the hTERT proximal promoter and enhanced the recruitment of the histone acetyltransferase p300 and histone H3 acetylation locally in A498 cells treated with hypoxia. Increased levels of hTERT mRNA were observed in two of three hypoxia-treated malignant glioma cell lines. However, HIF-1α stimulated whereas HIF-2α inhibited the hTERT promoter activity in these glioma cell lines. Ectopic expression of HIF-2α resulted in diminished hTERT expression in glioma cells. Collectively, HIF-1α activates hTERT and telomerase expression in both RCC and glioma cells, and HIF-2α enhances hTERT expression in RCC cells, whereas it represses the hTERT transcription in glioma cells. These findings reveal a complex relationship between HIF-1α/2α and hTERT/telomerase expression in malignant cells, which may have both biological and clinical implications. (Mol Cancer Res 2007;5(8):793–800)
(Dihydro)ceramide Synthase 1–Regulated Sensitivity to Cisplatin Is Associated with the Activation of p38 Mitogen-Activated Protein Kinase and Is Abrogated by Sphingosine Kinase 1
Authors: Min Junxia , Mesika Adi , Sivaguru Mayandi , Van Veldhoven Paul P. , Alexander Hannah , Futerman Anthony H. , Alexander Stephen 
Published: August 2007

Abstract
Resistance to chemotherapeutic drugs often limits their clinical efficacy. Previous studies have implicated the bioactive sphingolipid sphingosine-1-phosphate (S-1-P) in regulating sensitivity to cisplatin [cis-diamminedichloroplatinum(II)] and showed that modulating the S-1-P lyase can alter cisplatin sensitivity. Here, we show that the members of the sphingosine kinase (SphK1 and SphK2) and dihydroceramide synthase (LASS1/CerS1, LASS4/CerS4, and LASS5/CerS5) enzyme families each have a unique role in regulating sensitivity to cisplatin and other drugs. Thus, expression of SphK1 decreases sensitivity to cisplatin, carboplatin, doxorubicin, and vincristine, whereas expression of SphK2 increases sensitivity. Expression of LASS1/CerS1 increases the sensitivity to all the drugs tested, whereas LASS5/CerS5 only increases sensitivity to doxorubicin and vincristine. LASS4/CerS4 expression has no effect on the sensitivity to any drug tested. Reflecting this, we show that the activation of the p38 mitogen-activated protein (MAP) kinase is increased only by LASS1/CerS1, and not by LASS4/CerS4 or LASS5/CerS5. Cisplatin was shown to cause a specific translocation of LASS1/CerS1, but not LASS4/CerS4 or LASS5/CerS5, from the endoplasmic reticulum (ER) to the Golgi apparatus. Supporting the hypothesis that this translocation is mechanistically involved in the response to cisplatin, we showed that expression of SphK1, but not SphK2, abrogates both the increased cisplatin sensitivity in cells stably expressing LASS1/CerS and the translocation of the LASS1/CerS1. The data suggest that the enzymes of the sphingolipid metabolic pathway can be manipulated to improve sensitivity to the widely used drug cisplatin. (Mol Cancer Res 2007;5(8):801–12)
Ataxia Telangiectasia-Mutated–Dependent DNA Damage Checkpoint Functions Regulate Gene Expression in Human Fibroblasts
Authors: Zhou Tong , Chou Jeff , Zhou Yingchun , Simpson Dennis A. , Cao Feng , Bushel Pierre R. , Paules Richard S. , Kaufmann William K. 
Published: August 2007

Abstract
The relationships between profiles of global gene expression and DNA damage checkpoint functions were studied in cells from patients with ataxia telangiectasia (AT). Three telomerase-expressing AT fibroblast lines displayed the expected hypersensitivity to ionizing radiation (IR) and defects in DNA damage checkpoints. Profiles of global gene expression in AT cells were determined at 2, 6, and 24 h after treatment with 1.5-Gy IR or sham treatment and were compared with those previously recognized in normal human fibroblasts. Under basal conditions, 160 genes or expressed sequence tags were differentially expressed in AT and normal fibroblasts, and these were associated by gene ontology with insulin-like growth factor binding and regulation of cell growth. On DNA damage, 1,091 gene mRNAs were changed in at least two of the three AT cell lines. When compared with the 1,811 genes changed in normal human fibroblasts after the same treatment, 715 were found in both AT and normal fibroblasts, including most genes categorized by gene ontology into cell cycle, cell growth, and DNA damage response pathways. However, the IR-induced changes in these 715 genes in AT cells usually were delayed or attenuated in comparison with normal cells. The reduced change in DNA damage response genes and the attenuated repression of cell cycle–regulated genes may account for the defects in cell cycle checkpoint function in AT cells. (Mol Cancer Res 2007;5(8):813–22)
US–Russian Strategic Relations and the Structuration of Central Asia
Authors: Cutler Robert 
Published: August 2007

AbstractCentral Asia is only one of the core regional subsystems of international relations that constitute Central Eurasia. The others are Southwest Asia and South Asia. All three subsystems are mutually distinct and do not intersect. The years 1989-1994 saw the geopolitical enlargement of Southwest Asia into Greater Southwest Asia; 1995-2000, that of Central Asia into Greater Central Asia; and 2001-2006, that of South Asia into Greater South Asia. These "Greater" complements overlap, and their intersection is key to the future of international relations in Greater Central Asia and Central Eurasia as a whole. It is through their matrix that powers such as Russia and the United States (as well as China, India, Iran, Turkey) play out their search for influence in Central Asia proper.
The Iranian Revolution: The Multiple Contexts of the Iranian Revolution
Authors: Amineh  , Eisenstadt  
Published: August 2007

AbstractThe Iranian Islamic Revolution, the only continual regime constituted by a modern fundamentalist movement, shares many of the characteristics of the Great revolutions. The causes of the Iranian Revolution are indeed very similar to those of the classical ones—namely the breakdown of a modernizing autocracy torn by internal contradictions between various processes of economic and social modernization that gave rise to many new modernized economic and professional classes, but denying them any political autonomy, any autonomous access to the political center, at the same time uprooting them from wider sectors of peasant and urban population—very much in a rather typical third world way, pushing them into the slums of the cities. The Khomeini Revolution also developed in the context of the expansion of modernity, and it built on many of the structural and organizational aspects of modernity—especially of course in the use of the media and modern organizational methods for the mobilization of the masses. It was also fully imbued by some of the institutional and ideological premises of modernity. Not only did it adapt such modern political institutions as parliament or presidency—to which there is no reference in any pristine Islamic vision—but it did also emphasize in modern ways such themes as equality and political participation far beyond what could be found in such vision or visions. At the same time the Iranian ulama felt utterly alienated from the Shah's secular regime, and modernizing ideology. Their basic cosmological orientations were radically antimodern, or rather more exactly anti-Enlightenment and anti-Western. It was this distinct combination of modern and anti-Enlightenment and anti-Western cosmological visions; as developed in the framework of new globalizing and inter-civilizational visions; that distinguished the Iranian Islamic revolution from the classical ones, bringing out some of its paradoxical similarities within the different post-modern movements. Thus, indeed, the modern fundamentalist movements, in a way most fully epitomized in the Iranian revolution, as well as in somewhat different mode the communal religious movements, entail an important, even radical, shift in the discourse about the confrontation with modernity and in the conceptualization of the relation between the Western and non-Western civilizations, religions or societies—thus, paradoxically sharing many characteristics with the various "post-modern" movements.
Iranian Foreign Policy since the Iranian Islamic Revolution: 1979-2006
Authors: Rakel Eva Patricia 
Published: August 2007

AbstractThis article analyzes Iranian foreign policy since the Iranian Islamic revolution of 1979. The main questions to be dealt with are: what influences has the Iranian Islamic revolution had on foreign policy orientation and formulation of the Islamic Republic of Iran? What influences has Shi'ism had on foreign policy formulation in Iran? What impact have Supreme Leader Ayatollah Ruhollah Khomeini, and the three presidents Hojjatoleslam Ali Akbar Hashemi Rafsanjani, Hojjatoleslam Mohammad Khatami, and Mahmoud Ahmadinejad had on foreign policy orientation? Have there been major shifts in foreign policy orientation during their tenures or has the overall foreign policy approach that was introduced by Khomeini after the revolution in 1979 remained the same? The article will first discuss the history of Shi'ism in Iran and its impact on politics since the introduction of Islam as state religion in the beginning of the sixteenth century by the Safavid Empire. It will then give an introduction to power relations in Iran since the Iranian Islamic revolution and analyze foreign policy orientation in Iran in four phases: (1) from 1979 to 1989, when Khomeini was the Supreme Leader; (2) from 1989-1997, during the presidency of Rafsanjani; (3) from 1997-2005, during the presidency of Khatami; and (4) since Ahmadinejad's presidency began in 2005.
The Middle East's Democracy Deficit in Comparative Perspective
Authors: Kamrava Mehran 
Published: August 2007

AbstractThe Middle East's democracy deficit is a product of the patterns of political and economic development in the region. It is not because the region is predominantly Islamic or is somehow afflicted by purportedly undemocratic cultures. By itself, culture is not an impediment to transition to democracy as it is subject to influences from the larger polity, especially insofar as the economy and the initiatives of the state are concerned. Instead, transition to democracy is determined by the degree of society's autonomy from the state. This autonomy may result from the empowerment of society as a consequence of economic development, or the state elite's devolution of power to social actors and classes, or, more commonly, a combination of both. Assumptions about the inherently undemocratic nature of cultures such as Islamic and Confucian ones are fundamentally invalid. The key to understanding democratic transitions lies instead in the nature of state-society relations rather than the nature of society's norms and values in themselves.
The Turkish Political Economy: Globalization and Regionalism
Authors: Onder Nilgun 
Published: August 2007

AbstractSince the early 1980s, the Turkish economy has globalized via neoliberal reforms. Turkey's globalization entailed a fundamental shift from the inward-oriented, state-led industrialization that had characterized the Turkish political economy for decades to a strategy of export-led growth in an open market economy. Regionalism also became a major component of Turkey's globalization. In the post-Cold War era, the Turkish state has actively pursued multiple projects of regional economic integration. Regional projects are currently regarded as building blocks to Turkey's more successful participation in globalization. However, Turkey's neoliberal form of globalization so far has been characterized by major structural weaknesses, and it has resulted in recurrent economic crises.
Central Asia since the Dissolution of the Soviet Union: Economic Reforms and eir Impact on State-Society Relations
Authors: Pomfret Richard 
Published: August 2007

AbstractIn late 1991, with the sudden collapse of the Soviet Union, the five Central Asian republics became independent countries. The completely unexpected challenges of nation-building were superimposed on the transition from a centrally planned economy. Within the common bounds of resource-based economies and autocratic regimes, the five countries gradually became more differentiated as their governments introduced diverse national strategies for transition to a market-based economy. This article describes the different economic polices adopted by Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan and analyzes the outcomes.
New Twists, More Intricate Configurations: The Changing Israel-Palestinian Regional Security Complex
Authors: Lawson Fred 
Published: August 2007

AbstractPolicies adopted by Syria, Hizbullah, and Israel have generated a major transformation in the Israel-Palestinian regional security complex. In the months after the United States-led overthrow of the Ba'thi regime in Iraq in March 2003, each of these three leaderships confronted a severe domestic political-economic crisis, and reacted to the crisis in ways that not only heightened the potential for conflict in regional affairs but also transformed the regional security complex into a more extensive constellation of alliances and adversarial relations.