bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Analysis of
Plasmodium falciparum
Apical Membrane Antigen 1 Utilizing Interspecies Domains
Authors: Healer Julie , Triglia Tony , Hodder Anthony N. , Gemmill Alan W. , Cowman Alan F. 
Published: March 2005

ABSTRACT

Plasmodium falciparum
apical membrane antigen 1 (AMA1) is a leading malaria vaccine candidate whose function has not been unequivocally defined. Partial complementation of function can be achieved by exchanging the AMA1 of
P. falciparum
(PfAMA1) with that of
P. chabaudi
(PcAMA1). In this study, parasites expressing chimeric AMA1 proteins were created to identify domains of PfAMA1 critical in erythrocyte invasion and which are important immune targets. We report that specific chimeric AMA1 proteins containing domains I to III from PfAMA1 and PcAMA1 were able to complement PfAMA1 function in erythrocyte invasion. We demonstrate that domain III does not contain dominant epitope targets of antibodies raised against
Escherichia coli
expressed and refolded PfAMA1 ectodomain. Furthermore, we generated a parasite line in which the N-terminal
pro
region of PfAMA1 does not undergo proteolytic cleavage and show that its removal is necessary for PfAMA1 function.
Enterococcus faecalisTropism for the Kidneys in the Urinary Tract of C57BL/6J Mice
Authors: Kau Andrew L. , Martin Steven M. , Lyon William , Hayes Ericka , Caparon Michael G. , Hultgren Scott J. 
Published: March 2005

ABSTRACTEnterococcus faecalisis a gram-positive bacterium that can cause a variety of nosocomial infections of which urinary tract infections are the most common. These infections can be exceptionally difficult to treat because of drug resistance of manyE. faecalisisolates. Despite their troublesome nature, little is known about the host or bacterial factors necessary forE. faecalisto cause disease in the urinary tract. Using a mouse model of urinary tract infection, we have shown thatE. faecalisis capable of persisting in the kidneys of mice for at least 2 weeks. In contrast, bacterial titers from the bladders of the same mice were inconsistent and tended to be much lower than those recovered from the kidney. This preference for the kidney over the bladder is also observed in other clinicalE. faecalisstrains. Histologic examination of bladder and kidney tissues demonstrated thatE. faecalisinduced an inflammatory response in the kidney but not in the bladder. This inflammatory response was TLR2 independent and did not induce inflammatory markers typically associated with uropathogenicEscherichia coli. Using a competition assay, we demonstrated that a pyelonephritis clinical isolate had a growth advantage over a laboratory strain ofE. faecalisin the kidneys but not in the bladders of mice. Taken together, these results demonstrate thatE. faecalishas tropism for the kidneys in the urinary tracts of mice and that this system can be used to study factors involved in the pathogenesis of urinary tract infections.
Purification and Partial Characterization of a
Paracoccidioides brasiliensis
Protein with Capacity To Bind to Extracellular Matrix Proteins
Authors: González Angel , Gómez Beatriz L. , Diez Soraya , Hernández Orville , Restrepo Angela , Hamilton Andrew J. , Cano Luz E. 
Published: March 2005

ABSTRACT

Microorganisms adhere to extracellular matrix proteins by means of their own surface molecules.
Paracoccidioides brasiliensis
conidia have been shown to be capable of interacting with extracellular matrix proteins. We aimed at determining the presence of fungal proteins that could interact with extracellular matrix protein and, if found, attempt their purification and characterization. Various extracts were prepared from
P. brasiliensis
mycelial and yeast cultures (total homogenates, β-mercaptoethanol, and sodium dodecyl sulfate [SDS] extracts) and analyzed by ligand affinity assays with fibronectin, fibrinogen and laminin. Two polypeptides were detected in both fungal forms. SDS extracts that interacted with all the extracellular matrix protein were tested; their molecular masses were 19 and 32 kDa. Analysis of the N-terminal amino acid sequence of the purified 32-kDa mycelial protein showed substantial homology with
P. brasiliensis
,
Histoplasma capsulatum
, and
Neurospora crassa
hypothetical proteins. Additionally, a monoclonal antibody (MAb) produced against this protein recognized the 32-kDa protein in the SDS extracts of both fungal forms for immunoblot. Immunofluorescence analysis revealed that this MAb reacted not only with mycelia and yeast cells, but also with conidia, indicating that this protein was shared by the three fungal propagules. By immunoelectron microscopy, this protein was detected in the cell walls and in the cytoplasm. Both the 32-kDa purified protein and MAb inhibited the adherence of conidia to the three extracellular matrix proteins in a dose-dependent manner. These findings demonstrate the presence of two polypeptides capable of interacting with extracellular matrix proteins on the surface of
P. brasiliensis
propagules, indicating that there may be common receptors for laminin, fibronectin, and fibrinogen. These proteins would be crucial for initial conidial adherence and perhaps also in dissemination of paracoccidioidomycosis.
Role of Endothelin 1 in the Pathogenesis of Chronic Chagasic Heart Disease
Authors: Tanowitz Herbert B. , Huang Huan , Jelicks Linda A. , Chandra Madhulika , Loredo Maria L. , Weiss Louis M. , Factor Stephen M. , Shtutin Vitaliy , Mukherjee Shankar , Kitsis Richard N. , Christ George J. , Wittner Murray , Shirani Jamshid , Kisanuki Yaz Y. , Yanagisawa Masashi 
Published: March 2005

ABSTRACT

On the basis of previous observations, endothelin 1 (ET-1) has been suggested as contributing to the pathogenesis of Chagasic cardiomyopathy. Therefore, ET-1
flox/flox
;α-MHC-Cre(+) mice in which the ET-1 gene was deleted from cardiac myocytes and ET-1
flox/flox
;Tie 2 Cre(+) mice in which the ET-1 gene was deleted from endothelial cells were infected with
Trypanosoma cruzi
. Genetic controls for these cell-specific ET-1 knockout mice were used. Ninety percentage of all mice survived acute infection with the Brazil strain and were evaluated 130 days postinfection. Inflammation and fibrosis were observed in all infected mice; however, fibrosis was reduced in ET-1
flox/flox
;α-MHC-Cre(+) mice. Cardiac magnetic resonance imaging revealed that infection resulted in a significant increase in right ventricular internal diameter (RVID) in all mice except ET-1
flox/flox
;α-MHC-Cre(+) mice; i.e., RVID was not changed in infected ET-1
flox/flox
;α-MHC-Cre(+) mice. Echocardiography of the left ventricle demonstrated increased left ventricular end-diastolic diameter, reduced fractional shortening, and decreased relative wall thickness in infected mice. However, the magnitude of the changes was significantly less in ET-1
flox/flox
;α-MHC-Cre(+) mice compared to other groups. These data provide further evidence of a role for ET-1, particularly cardiac myocyte-derived ET-1, in the pathogenesis of chronic Chagasic cardiomyopathy.
Novel Mouse Model of ChronicPseudomonas aeruginosaLung Infection Mimicking Cystic Fibrosis
Authors: Hoffmann Nadine , Rasmussen Thomas Bovbjerg , Jensen PeterØstrup , Stub Charlotte , Hentzer Morten , Molin Søren , Ciofu Oana , Givskov Michael , Johansen Helle Krogh , Høiby Niels 
Published: March 2005

ABSTRACTPseudomonas aeruginosacauses a chronic infection in the lungs of cystic fibrosis (CF) patients by establishing an alginate-containing biofilm. The infection has been studied in several animal models; however, most of the models required artificial embedding of the bacteria. We present here a new pulmonary mouse model without artificial embedding. The model is based on a stable mucoid CF sputum isolate (NH57388A) with hyperproduction of alginate due to a deletion inmucAand functionalN-acylhomoserine lactone (AHL)-based quorum-sensing systems. Chronic lung infection could be established in both CF mice (CftrtmlUnc−/−) and BALB/c mice, as reflected by the detection of a high number ofP. aeruginosaorganisms in the lung homogenates at 7 days postinfection and alginate biofilms, surrounded by polymorphonuclear leukocytes in the alveoli. In comparison, both an AHL-producing nonmucoid revertant (NH57388C) from the mucoid isolate (NH57388A) and a nonmucoid isolate (NH57388B) deficient in AHL were almost cleared from the lungs of the mice. This model, in whichP. aeruginosais protected against the defense system of the lung by alginate, is similar to the clinical situation. Therefore, the mouse model provides an improved method for evaluating the interaction between mucoidP. aeruginosa, the host, and antibacterial therapy.
Shiga Toxin Is Transported from the Endoplasmic Reticulum following Interaction with the Luminal Chaperone HEDJ/ERdj3
Authors: Yu Min , Haslam David B. 
Published: March 2005

ABSTRACT
Shiga toxin (Stx) follows a complex intracellular pathway in order to kill susceptible cells. After binding to cell surface glycolipids, the toxin is internalized and trafficked in retrograde fashion to the endoplasmic reticulum (ER). From the ER lumen, the toxin must gain access to the cytoplasm, where it enzymatically inactivates the 28S rRNA, inhibiting protein synthesis. The host molecules involved in this pathway and the mechanisms utilized by the toxin to access the cytoplasm from the ER are largely unknown. We found that Stx is capable of energy-dependent transport across the ER lumen, as has recently been demonstrated for the cholera and ricin toxins. Genetic screening for molecules involved in Shiga toxin trafficking yielded a cDNA encoding a prematurely truncated protein. Characterization of this cDNA revealed that it encodes a novel Hsp40 chaperone, designated HEDJ or ERdj3, localized to the ER lumen, where it interacts with BiP, a molecule known to be involved in protein retrotranslocation out of the ER. We demonstrated that within the ER lumen Stx interacts with HEDJ and other chaperones known to be involved in retrotranslocation of proteins across the ER membrane. Moreover, sequential immunoprecipitation revealed that Shiga toxin was present in a complex that included HEDJ and Sec61, the translocon through which proteins are retrotranslocated to the cytoplasm. These findings suggest that HEDJ is a component of the ER quality control system and that Stx utilizes HEDJ and other ER-localized chaperones for transport from the ER lumen to the cytosol.
Designer Arrays for Defined Mutant Analysis To Detect Genes Essential for Survival of
Mycobacterium tuberculosis
in Mouse Lungs
Authors: Lamichhane Gyanu , Tyagi Sandeep , Bishai William R. 
Published: March 2005

ABSTRACT

The mechanisms by which
Mycobacterium tuberculosis
elicits disease are complex, involving a large repertoire of bacterial genes that are required for in vivo growth and survival. To identify such genes, we utilized a high-throughput microarray detection method to rapidly screen hundreds of unique, genotypically defined transposon mutants for in vivo survival with a high degree of specificity and sensitivity. Thirty-one
M. tuberculosis
genes were found to be required for in vivo survival in mouse lungs. These genes are involved in a broad range of activities, including metabolism, cell wall functions, and regulation. Our screen included 11 of the 12 known members of the mycobacterial membrane protein (mmpL) family genes, and mutation of 6 of these genes—
mmpL4
,
mmpL5
,
mmpL7
,
mmpL8
,
mmpL10
, and
mmpL11
—severely compromised the ability of the mutants to multiply in mouse lungs. Most of the 31 genes are conserved in other pathogenic mycobacteria, including
M. leprae
and
M. bovis
, suggesting that a core of basic in vivo survival mechanisms may be highly conserved despite the divergent human pathology caused by members of the mycobacterial genus. Of the 31 genes reported here, 17 have not been previously described to be involved in in vivo growth and survival of
M. tuberculosis.
Isocitrate Lyase (AceA) Is Required for Salmonella Persistence but Not for Acute Lethal Infection in Mice
Authors: Fang Ferric C. , Libby Stephen J. , Castor Margaret E. , Fung Angela M. 
Published: March 2005

ABSTRACT

Isocitrate lyase is required for fatty acid utilization via the glyoxylate shunt. Although isocitrate lyase is essential for
Salmonella
persistence during chronic infection, it is dispensable for acute lethal infection in mice. Substrate availability in the phagosome appears to evolve over time, with increasing fatty acid dependence during chronic infection.
The Mannose Receptor Mediates the Cellular Immune Response in Human Coccidioidomycosis
Authors: Ampel Neil M. , Nelson Daniel K. , Li Lijin , Dionne Sara O. , Lake Douglas F. , Simmons Keira A. , Pappagianis Demosthenes 
Published: March 2005

ABSTRACT
Mannose is the predominant monosaccharide in the coccidioidal antigen preparation T27K. Mannan and anti-CD206 antibody significantly decreased the surface expression of mannose receptor (MR) on adherent peripheral blood mononuclear cells and reduced the interleukin-2 (IL-2) release induced by T27K. These data suggest that MR mediates IL-2 release by T27K.
Nonopsonic Phagocytosis of Erythrocytes Infected with Ring-StagePlasmodium falciparum
Authors: Ayi Kodjo , Patel Samir N. , Serghides Lena , Smith Todd G. , Kain Kevin C. 
Published: March 2005

ABSTRACTRing-stage parasitized erythrocytes (RPEs) were demonstrated to interact with effector cells of the innate immune system. With receptor blockade studies and CD36-null macrophages, human and murine macrophages were shown to phagocytose RPEs through the pattern recognition receptor CD36. These in vitro data implicate scavenger receptors in the clearance of RPEs.
Leishmania majorModulates Chemokine and Chemokine Receptor Expression by Dendritic Cells and Affects Their Migratory Capacity
Authors: Steigerwald Mario , Moll Heidrun 
Published: March 2005

ABSTRACTDendritic cells (DC) both produce and respond to chemokines. We examined the profiles of chemokines and chemokine receptors expressed by DC and their chemotactic response after interaction withLeishmania major. Expression of the chemokine receptors CCR2 and CCR5 by DC and their responsiveness to the respective ligands, CCL2 and CCL3, were downregulated, while the level of CCR7 and the DC response to its ligand CCL21 were enhanced. These parasite-induced alterations were observed with DC fromL. major-resistant and -susceptible mice. In contrast, expression of the chemokine CXCL10 was elicited only in DC fromL. major-resistant mice.
Intermediate Realms of Law: Corporate Groups and Rulers in Medieval India
Authors: Davis Donald 
Published: March 2005

AbstractThe laws of corporate groups such as merchants, traders, religious specialists, soldiers, etc. are examined on the basis of both the normative Hindu legal texts and epigraphical sources from various parts of India. Other recent studies arguing that medieval India experienced an increasing integration of polity and society over larger core areas are corroborated from the perspective of law and legal institutions. Methodological and theoretical propositions are also raised to argue that Hindu legal texts, known as Dharmaśastra, are essential to any history of law and society in medieval India, but only when their nature and purpose are properly understood. Les lois des corps sociaux, comme les marchands, les négociants, les experts religieux, ou les soldats, sont examinées d'après les textes normatifs du droit hindou ancien, et aussi selon des sources épigraphiques venant des diverses régions de l'Inde. D'autres études récentes qui affirment que l'Inde médiévale a connu une intégration croissante entre régime et société dans des domaines centralisés plus étendus sont ici con firmées par le biais du droit et des institutions légales. Des arguments méthodologiques et théoriques sont aussi soulevés pour soutenir que les textes légals hindous, connus sous le nom de Dharmaśastra, sont fondamentals à toute histoire du droit et de la société dans l'Inde médiévale, mais seulement quand leur nature et leur objet sont bien compris.
Meier, Miracle and Multiple Attestation
Authors: Eve Eric 
Published: March 2005

AbstractThe use of criteria in historical Jesus research gives the enterprise an appearance of scientific objectivity that may be deceptive. A particular case in point is the use of multiple attestation to establish the near certainty that the historical Jesus was a healer and exorcist (as, for example, J.P. Meier argues). Logically, there is little reason why multiple attestation alone should indicate historical reliability, and there may not be as many useful independent sources for Jesus’ miracles as Meier supposes. Jesus may well have been a healer and exorcist, but if so, this needs to be established on other grounds.
Presuppositions and Procedures in the Study of the ‘Historical Jesus’: Or, Why I Decided Not to be a ‘Historical Jesus’ Scholar
Authors: Willitts Joel 
Published: March 2005

AbstractThis article provides a detailed description of the presuppositions and procedures of a representative group of six scholars currently contributing to the study of the ‘historical Jesus’. The intention of the study was to draft a ‘handbook’, a ‘recipe’, of the best methods and the surest presuppositions for achieving the result of a solid historical conclusion about Jesus. What resulted from the project was not what had been hoped. In fact, what resulted was a deep scepticism about the quest, at least as it is currently being conducted. Though, admittedly, not offering solutions, this article seeks to raise questions about the real potential and usefulness of any quest for the so-called ‘historical Jesus’.
‘Rooted in Detachment’: Transfiguration as Narrative, Worship and Community of Faith
Authors: Stevenson Kenneth 
Published: March 2005

AbstractThe Transfiguration is recorded in all three synoptic gospels, and points the onlookers towards the cross. The article looks at these narratives, with their variations, and then examines the way in which expositors and preachers, patristic, medieval and modern, have applied the Transfiguration to Christian living. Important are the two quite distinct ways in which the narrative has been used liturgically, in the Latin West, originally as a feature of Lenten preaching, and in the East as a festival in its own right on August 6th. Drawing the two traditions of interpretation and worship together, it is possible to see fresh ways of understanding the impact of the Transfiguration on the Church’s self-understanding: the tension between continuity and discontinuity; the transformation of the three uncomprehending apostles; and the hidden but mobile character of the community of faith. The Transfiguration emerges as a truth that illuminates Christian discipleship at its most profound.
The Church of Jesus Christ: An Introduction
Authors: Beintker Michael 
Published: March 2005

AbstractThis paper focuses on those points in the study The Church of Jesus Christ which may be important for dialogue on ecclesiological questions between the Community of Protestant Churches in Europe (CPCE) and the Anglican Churches in Europe. After a short account of the process of coming into being of this study, it summarizes its most important basic theological insights. Then it focuses on the questions of ministry and episkope and concludes with some remarks on the understanding of church unity in the context of the document.
Inhibition of CD4+25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide
Authors: Lutsiak M. E. Christine , Semnani Roshanak T. , De Pascalis Roberto , Kashmiri Syed V. S. , Schlom Jeffrey , Sabzevari Helen 
Published: March 2005

AbstractRegulatory T cells (TREGs) control the key aspects of tolerance and play a role in the lack of antitumor immune responses. Cyclophosphamide (CY) is a chemotherapeutic agent with a dose-dependent, bimodal effect on the immune system. Although a previous study demonstrated that CY reduces the number of TREGs, the mechanism involved in this process has yet to be defined. In this report, it is established that low-dose CY not only decreases cell number but leads to decreased functionality of TREGs. CY treatment enhances apoptosis and decreases homeostatic proliferation of these cells. Expression of GITR and FoxP3, which are involved in the suppressive activity of TREGs, is down-regulated after CY administration, though the level of expression varies depending on the time studied. This is the first report demonstrating that CY, in addition to decreasing cell number, inhibits the suppressive capability of TREGs. The relevance of the loss of suppressor functionality and the changes in gene expression are further discussed.
Triggering of OX40 (CD134) on CD4+CD25+ T cells blocks their inhibitory activity: a novel regulatory role for OX40 and its comparison with GITR
Authors: Valzasina Barbara , Guiducci Cristiana , Dislich Heidrun , Killeen Nigel , Weinberg Andrew D. , Colombo Mario P. 
Published: March 2005

AbstractOX40 (CD134) is a member of the tumor necrosis factor (TNF) receptor family that is transiently expressed on T cells after T-cell receptor (TCR) ligation. Both naive and activated CD4+CD25+ regulatory T cells (T reg's) express OX40 but its functional role has not been determined. Since glucocorticoid-induced tumor necrosis factor receptor (GITR), a related TNF receptor family member, influences T reg function, we tested whether OX40 might have similar effect. Triggering either GITR or OX40 on T reg's using agonist antibodies inhibited their capacity to suppress and restored effector T-cell proliferation, interleukin-2 (IL-2) gene transcription and cytokine production. OX40 abrogation of T reg suppression was confirmed in vivo in a model of graft-versus-host disease (GVHD). In a fully allogeneic C57BL/6&gt;BALB/c bone marrow transplantation, GVHD was lethal unless T reg's were cotransferred with the bone marrow and effector T cells. Strikingly, T reg suppression of GVHD was abrogated either by intraperitoneal injection of anti-OX40 or anti-GITR monoclonal antibodies (mAbs) immediately after transfer, or by in vitro pretreatment of T reg's with the same mAbs before transfer. Cumulatively, the results suggest that in addition to controlling memory T-cell numbers, OX40 directly controls T reg–mediated suppression.
Endothelial tetraspanin microdomains regulate leukocyte firm adhesion during extravasation
Authors: Barreiro Olga , Yáñez-Mó María , Sala-Valdés Mónica , Gutiérrez-López María Dolores , Ovalle Susana , Higginbottom Adrian , Monk Peter N. , Cabañas Carlos , Sánchez-Madrid Francisco 
Published: March 2005

AbstractTetraspanins associate with several transmembrane proteins forming microdomains involved in intercellular adhesion and migration. Here, we show that endothelial tetraspanins relocalize to the contact site with transmigrating leukocytes and associate laterally with both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Alteration of endothelial tetraspanin microdomains by CD9–large extracellular loop (LEL)–glutathione S–transferase (GST) peptides or CD9/CD151 siRNA oligonucleotides interfered with ICAM-1 and VCAM-1 function, preventing lymphocyte transendothelial migration and increasing lymphocyte detachment under shear flow. Heterotypic intercellular adhesion mediated by VCAM-1 or ICAM-1 was augmented when expressed exogenously in the appropriate tetraspanin environment. Therefore, tetraspanin microdomains have a crucial role in the proper adhesive function of ICAM-1 and VCAM-1 during leukocyte adhesion and transendothelial migration.