bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasminogen activators and plasminogen activator inhibitors in gingival crevicular fluid of cyclosporin A‐treated patients
Authors: Buduneli Nurcan , Buduneli Eralp , Çιnar Sema , Atilla Gül , Lappin David , Kinane Denis 
Published: June 2004

AbstractBackground: The plasminogen activator (PA) system plays many roles in the inflammatory process and tissue remodelling and repair and is considered to play a significant role in periodontal tissue destruction and healing. The aim of this study was to evaluate the role of the PA system in cyclosporin A (CsA)‐induced gingival overgrowth in renal transplant patients.Methods: Eighteen renal transplant patients exhibiting moderate to severe CsA‐induced gingival overgrowth, 10 other renal transplant patients receiving CsA therapy but showing no sign of CsA‐induced gingival overgrowth (CsA‐H), 16 chronic gingivitis patients (CG) and 16 systemically and periodontally healthy control subjects (H) were included in the study. Gingival crevicular fluid (GCF) samples were obtained from four randomly selected sites in each subject with the exception of the CsA‐induced gingival overgrowth group, where four GCF samples were harvested from sites with severe overgrowth (CsA GO+) and from four sites without any gingival overgrowth (CsA GO−). The GCF levels of albumin, tissue‐type plasminogen activator (t‐PA), urokinase‐type plasminogen activator (u‐PA), plasminogen activator inhibitor 1 (PAI‐1) and plasminogen activator inhibitor 2 (PAI‐2) were analysed by enzyme‐linked immunosorbent assay. The results were tested for statistical differences.Results: In CsA GO+ sites t‐PA levels were significantly elevated in comparison with gingivitis and healthy sites, while PAI‐2 levels in these sites showed statistically significant differences only with CsA‐H and gingivitis sites (p<0.05). The levels of t‐PA and PAI‐2 were significantly higher in CsA GO− sites compared with those of CsA‐H, gingivitis and healthy sites (p<0.05). The levels of u‐PA and PAI‐1 failed to show significant differences between the study groups.Conclusions: The findings of the present study indicate alterations in GCF t‐PA and PAI‐2 levels in CsA‐induced gingival overgrowth and might suggest involvement of the plasminogen activating system in the pathogenesis of this side‐effect of CsA therapy. However, to what extent these molecules contribute to the pathogenesis of CsA‐induced gingival overgrowth remains to be determined.
Alterations in expression of retinoid receptor β and p53 in oral submucous fibrosis
Authors: Kaur J , Chakravarti N , Mathur M , Srivastava A , Ralhan R 
Published: June 2004

Objective:  Knowledge of the molecular pathogenesis of oral submucous fibrosis (OSF), a potentially malignant condition with high risk of transition to oral cancer, is meagre. Alterations in the expression of retinoic acid receptor β (RARβ) and tumor suppressor gene, p53 are early events in oral tumorigenesis. The aim of this study was to investigate the alterations in the expression of RARβ and p53 in OSF lesions and determine their association with disease pathogenesis.Methods:  The expression of RARβ and p53 proteins was analyzed by immunohistochemistry in 50 cases of OSF and 30 histologically normal oral tissues.Results:  No detectable RARβ expression was observed in 35 of 50 (70%) OSF cases. p53 protein accumulation was observed in 24 of 50 (48%) OSF cases analyzed. Thirty‐six percent OSF lesions showed loss of RARβ and p53 overexpression. Interestingly, 41 of 50 (82%) of OSF lesions showed altered expression of at least one of these two proteins.Conclusion:  Altered expression of either RARβ or p53 in majority of OSF lesions suggests their association with disease pathogenesis and warrants follow‐up to determine whether OSF lesions harboring concomitant alterations in RARβ and p53 are at a high risk of transition to malignancy.
Homing Endonucleases Encoded by Germ Line-Limited Genes in
Tetrahymena thermophila
Have APETELA2 DNA Binding Domains
Authors: Wuitschick Jeffrey D. , Lindstrom Paul R. , Meyer Alison E. , Karrer Kathleen M. 
Published: June 2004

ABSTRACT

Three insertion elements were previously found in a family of germ line-limited mobile elements, the Tlr elements, in the ciliate
Tetrahymena
. Each of the insertions contains an open reading frame (ORF). Sequence analysis of the deduced proteins encoded by the elements suggests that they are homing endonucleases. The genes are designated
TIE1-1
,
TIE2-1
, and
TIE3-1
for
Tetrahymena
insertion-homing endonuclease. The endonuclease motif occupies the amino terminal half of each TIE protein. The C-terminal regions of the proteins are similar to the APETELA2 DNA binding domain of plant transcription factors. The TIE1 and TIE3 elements belong to families of repeated sequences in the germ line micronuclear genome. Comparison of the genes and the deduced proteins they encode suggests that there are at least two distinct families of homing endonuclease genes, each of which appears to be preferentially associated with a specific region of the Tlr elements. The TIE1 and TIE3 elements and their cognates undergo programmed elimination from the developing somatic macronucleus of
Tetrahymena
. The possible role of homing endonuclease-like genes in the DNA breakage step in developmentally programmed DNA elimination in
Tetrahymena
is discussed.
Inducible Defense Mechanism against Nitric Oxide inCandida albicans
Authors: Ullmann Breanna D. , Myers Hadley , Chiranand Wiriya , Lazzell Anna L. , Zhao Qiang , Vega Luis A. , Lopez-Ribot Jose L. , Gardner Paul R. , Gustin Michael C. 
Published: June 2004

ABSTRACTThe yeastCandida albicansis an opportunistic pathogen that threatens patients with compromised immune systems. Immune cell defenses againstC. albicansare complex but typically involve the production of reactive oxygen species and nitrogen radicals such as nitric oxide (NO) that damage the yeast or inhibit its growth. WhetherCandidadefends itself against NO and the molecules responsible for this defense have yet to be determined. The defense against NO in various bacteria and the yeastSaccharomyces cerevisiaeinvolves an NO-scavenging flavohemoglobin. TheC. albicansgenome contains three genes encoding flavohemoglobin-related proteins,CaYHB1,CaYHB4, andCaYHB5. To assess their roles in NO metabolism, we constructed strains lacking each of these genes and demonstrated that just one,CaYHB1, is responsible for NO consumption and detoxification. InC. albicans, NO metabolic activity andCaYHB1mRNA levels are rapidly induced by NO and NO-generating agents. Loss ofCaYHB1increases the sensitivity ofC. albicansto NO-mediated growth inhibition. In mice, infections withCandidastrains lackingCaYHB1still resulted in lethality, but virulence was decreased compared to that in wild-type strains. Thus,C. albicanspossesses a rapid, specific, and highly inducible NO defense mechanism involving one of three putative flavohemoglobin genes.
Cdc42p GTPase Regulates the Budded-to-Hyphal-Form Transition and Expression of Hypha-Specific Transcripts in
Candida albicans
Authors: vandenBerg Alysia L. , Ibrahim Ashraf S. , Edwards John E. , Toenjes Kurt A. , Johnson Douglas I. 
Published: June 2004

ABSTRACT

The yeast
Candida albicans
is a major opportunistic pathogen of immunocompromised individuals. It can grow in several distinct morphological states, including budded and hyphal forms, and the ability to make the dynamic transition between these forms is strongly correlated with virulence. Recent studies implicating the Cdc42p GTPase in hypha formation relied on
cdc42
mutations that affected the mitotic functions of the protein, thereby precluding any substantive conclusions about the specific role of Cdc42p in the budded-to-hypha-form transition and virulence. Therefore, we took advantage of several
Saccharomyces cerevisiae cdc42
mutants that separated Cdc42p's mitotic functions away from its role in filamentous growth. The homologous
cdc42-S26I
,
cdc42-E100G
, and
cdc42-S158T
mutations in
C. albicans
Cdc42p caused a dramatic defect in the budded-to-hypha-form transition in response to various hypha-inducing signals without affecting normal budded growth, strongly supporting the conclusion that Cdc42p has an integral function in orchestrating the morphological transition in
C. albicans
. In addition, the
cdc42-S26I
and
cdc42-E100G
mutants demonstrated a reduced ability to damage endothelial cells, a process that is strongly correlated to virulence. The three mutants also had reduced expression of several hypha-specific genes, including those under the regulation of the Efg1p transcription factor. These data indicate that Cdc42p-dependent signaling pathways regulate the budded-to-hypha-form transition and the expression of hypha-specific genes.
The Gβ-Subunit-Encoding Gene
bpp1
Controls Cyclic-AMP Signaling in
Ustilago maydis
Authors: Müller Philip , Leibbrandt Andreas , Teunissen Hedwich , Cubasch Stephanie , Aichinger Christian , Kahmann Regine 
Published: June 2004

ABSTRACT

In the phytopathogenic fungus
Ustilago maydis
, fusion of haploid cells is a prerequisite for infection. This process is controlled by a pheromone-receptor system. The receptors belong to the seven-transmembrane class that are coupled to heterotrimeric G proteins. Of four Gα subunits in
U. maydis
, only
gpa3
has a function during mating and cyclic AMP (cAMP) signaling. Activation of the cAMP cascade induces pheromone gene expression; however, it does not lead to the induction of conjugation tubes seen after pheromone stimulation. To investigate the possibility that a Gβ subunit participates in pheromone signaling, we isolated the single β subunit gene,
bpp1
, from
U. maydis. bpp1
deletion mutants grew filamentously and showed attenuated pheromone gene expression, phenotypes associated with
Δgpa3
strains. In addition, a constitutively active allele of
gpa3
suppressed the phenotype of the
bpp1
deletion strains. We suggest that Bpp1 and Gpa3 are components of the same heterotrimeric G protein acting on adenylyl cyclase. Interestingly, while
Δgpa3
strains are impaired in pathogenicity, Δ
bpp1
mutants are able to induce plant tumors. This could indicate that Gpa3 operates independently of Bpp1 during pathogenic development.
Functional Interaction between Class II Histone Deacetylases and ICP0 of Herpes Simplex Virus Type 1
Authors: Lomonte Patrick , Thomas Joëlle , Texier Pascale , Caron Cécile , Khochbin Saadi , Epstein Alberto L. 
Published: June 2004

ABSTRACT

This study describes the physical and functional interactions between ICP0 of herpes simplex virus type 1 and class II histone deacetylases (HDACs) 4, 5, and 7. Class II HDACs are mainly known for their participation in the control of cell differentiation through the regulation of the activity of the transcription factor MEF2 (myocyte enhancer factor 2), implicated in muscle development and neuronal survival. Immunofluorescence experiments performed on transfected cells showed that ICP0 colocalizes with and reorganizes the nuclear distribution of ectopically expressed class I and II HDACs. In addition, endogenous HDAC4 and at least one of its binding partners, the corepressor protein SMRT (for silencing mediator of retinoid and thyroid receptor), undergo changes in their nuclear distribution in ICP0-transfected cells. As a result, during infection endogenous HDAC4 colocalizes with ICP0. Coimmunoprecipitation and glutathione
S
-transferase pull-down assays confirmed that class II but not class I HDACs specifically interacted with ICP0 through their amino-terminal regions. This region, which is not conserved in class I HDACs but homologous to the MITR (MEF2-interacting transcription repressor) protein, is responsible for the repression, in a deacetylase-independent manner, of MEF2 by sequestering it under an inactive form in the nucleus. Consequently, we show that ICP0 is able to overcome the HDAC5 amino-terminal- and MITR-induced MEF2A repression in gene reporter assays. This is the first report of a viral protein interacting with and controlling the repressor activity of class II HDACs. We discuss the putative consequences of such an interaction for the biology of the virus both during lytic infection and reactivation from latency.
Identification of the Human Rhinovirus Serotype 1A Binding Site on the Murine Low-Density Lipoprotein Receptor by Using Human-Mouse Receptor Chimeras
Authors: Herdy Barbara , Snyers Luc , Reithmayer Manuela , Hinterdorfer Peter , Blaas Dieter 
Published: June 2004

ABSTRACT

Human rhinovirus serotype 1A (HRV1A) binds more strongly to the mouse low-density lipoprotein receptor (LDLR) than to the human homologue (M. Reithmayer, A. Reischl, L. Snyers, and D. Blaas, J. Virol.
76:
6957-6965, 2002). Here, we used this fact to determine the binding site of HRV1A by replacing selected ligand binding modules of the human receptor with the corresponding ligand binding modules of the mouse receptor. The chimeric proteins were expressed in mouse fibroblasts deficient in endogenous LDLR and LDLR-related protein, both used by minor group HRVs for cell entry. Binding was assessed by virus overlay blots, by immunofluorescence microscopy, and by measuring cell attachment of radiolabeled virus. Replacement of ligand binding repeat 5 of the human LDLR with the corresponding mouse sequence resulted in a substantial increase in HRV1A binding, whereas substitution of repeats 3 and 4 was without effect. Replacement of human receptor repeats 1 and 2 with the murine homologues also increased virus binding. Finally, murine receptor modules 1, 2, and 5 simultaneously introduced into the human receptor resulted in HRV1A binding indistinguishable from mouse wild-type receptor. Thus, repeats 1 and/or 2 and repeat 5 are involved in HRV1A attachment. Changing CDG

GP

D in the acidic cluster of module 5 in the human receptor to CDG

EA

D present in the mouse receptor led to substantially increased binding of HRV1A, indicating an important role of the glutamate residue in HRV1A recognition.
Complete DNA Sequence Analyses of the First Two Varicella-Zoster Virus Glycoprotein E (D150N) Mutant Viruses Found in North America: Evolution of Genotypes with an Accelerated Cell Spread Phenotype
Authors: Grose Charles , Tyler Shaun , Peters Geoff , Hiebert Joanne , Stephens Gwen M. , Ruyechan William T. , Jackson Wallen , Storlie Johnathan , Tipples Graham A. 
Published: June 2004

ABSTRACT
Varicella-zoster virus (VZV) is considered to be one of the most genetically stable of all the herpesviruses. Yet two VZV strains with a D150N missense mutation within the gE glycoprotein were isolated in North America in 1998 and 2002. The mutant strains have an accelerated cell spread phenotype, which distinguishes them from all wild-type and laboratory viruses. Since the VZV genome contains 70 additional open reading frames (ORFs), the possibility existed that the phenotypic change was actually due to an as-yet-undiscovered mutation or deletion elsewhere in the genome. To exclude this hypothesis, the entire genomes of the two mutant viruses were sequenced and found to contain 124,883 (VZV-MSP) and 125,459 (VZV-BC) nucleotides. Coding single-nucleotide polymorphisms (SNPs) were identified in 14 ORFs. One missense mutation was discovered in gH, but none was found in gB, gI, gL, or gK. There were no coding SNPs in the major regulatory protein ORF 62. One polymorphism was discovered which could never have been anticipated based on current knowledge of herpesvirus genomics, namely, the origins of replication differed from those in the prototype strain but not in a manner expected to affect cell spread. When the two complete mutant VZV sequences were surveyed in their entirety, the most reasonable conclusion was that the increased cell spread phenotype was dependent substantially or solely on the single D150N polymorphism in glycoprotein gE. The genomic results also expanded the evolutionary database by identifying which VZV ORFs were more likely to mutate over time.
Critical Role of CD4 T Cells in an Antibody-Independent Mechanism of Vaccination against Gammaherpesvirus Latency
Authors: McClellan James Scott , Tibbetts Scott A. , Gangappa Shivaprakash , Brett Kelly A. , Virgin Herbert W. 
Published: June 2004

ABSTRACTWe have previously demonstrated that it is possible to effectively vaccinate against long-term murine gammaherpesvirus 68 (γHV68) latency by using a reactivation-deficient virus as a vaccine (S. A. Tibbetts, J. S. McClellan, S. Gangappa, S. H. Speck, and H. W. Virgin IV, J. Virol. 77:2522-2529, 2003). Immune antibody was capable of recapitulating aspects of this vaccination. This led us to determine whether antibody is required for vaccination against latency. Using mice lacking antigen-specific antibody responses, we demonstrate here that antibody and B cells are not required for vaccination against latency. We also show that surveillance of latent infection in normal animals depends on CD4 and CD8 T cells, suggesting that T cells might be capable of preventing the establishment of latency. In the absence of an antibody response, CD4 T cells but not CD8 T cells are required for effective vaccination against latency in peritoneal cells, while either CD4 or CD8 T cells can prevent the establishment of splenic latency. Therefore, CD4 T cells play a critical role in immune surveillance of gammaherpesvirus latency and can mediate vaccination against latency in the absence of antibody responses.
Postinternalization Inhibition of Adenovirus Gene Expression and Infectious Virus Production in Human T-Cell Lines
Authors: McNees Adrienne L. , Mahr Jeff A. , Ornelles David , Gooding Linda R. 
Published: June 2004

ABSTRACT
Detection of adenovirus DNA in human tonsillar T cells in the absence of active virus replication suggests that T cells may be a site of latency or of attenuated virus replication in persistently infected individuals. The lytic replication cycle of Ad5 in permissive epithelial cells (A549) was compared to the behavior of Ad5 in four human T-cell lines, Jurkat, HuT78, CEM, and KE37. All four T-cell lines expressed the integrin coreceptors for Ad2 and Ad5, but only Jurkat and HuT78 express detectable surface levels of the coxsackie adenovirus receptor (CAR). Jurkat and HuT78 cells supported full lytic replication of Ad5, albeit at a level ∼10% of that of A549, while CAR-transduced CEM and KE37 cells (CEM-CARhi and KE37-CARhi, respectively) produced no detectable virus following infection. All four T-cell lines bind and internalize fluorescently labeled virus. In A549, Jurkat, and HuT78 cells, viral proteins were detected in 95% of cells. In contrast, only a small subpopulation of CEM-CARhi and KE37-CARhi cells contained detectable viral proteins. Interestingly, Jurkat and HuT78 cells synthesize four to six times more copies of viral DNA per cell than did A549 cells, indicating that these cells produce infectious virions with much lower efficiency than A549. Similarly, CEM-CARhi and KE37-CARhi cells, which produce no detectable infectious virus, synthesize three times more viral genomes per cell than A549. The observed blocks to adenovirus gene expression and replication in all four human T-cell lines may contribute to the maintenance of naturally occurring persistent adenovirus infections in human T cells.
Integrin α
v
β
6
Is an RGD-Dependent Receptor for Coxsackievirus A9
Authors: Williams Çiğdem H. , Kajander Tommi , Hyypiä Timo , Jackson Terry , Sheppard Dean , Stanway Glyn 
Published: June 2004

ABSTRACT

Coxsackievirus A9 (CAV9), a member of the
Enterovirus
genus of
Picornaviridae
, is a common human pathogen and is one of a significant number of viruses containing a functional arginine-glycine-aspartic acid (RGD) motif in one of their capsid proteins. Previous studies identified the RGD-recognizing integrin α
v
β
3
as its cellular receptor. However, integrin α
v
β
6
has been shown to be an efficient receptor for another RGD-containing picornavirus, foot-and-mouth disease virus (FMDV). In view of the similarity in sequence context of the RGD motifs in CAV9 and FMDV, we investigated whether α
v
β
6
can also serve as a receptor for CAV9. We found that CAV9 can bind to purified α
v
β
6
and also to SW480 cells transfected with β
6
cDNA, allowing expression of α
v
β
6
on their surface, but it cannot bind to mock-transfected cells. In addition, a higher yield of CAV9 was obtained in β
6
-expressing cells than in mock-transfected cells. There was no similar enhancement in infection with an RGD-less CAV9 mutant. We also found β
6
on the surface of GMK cells, a cell line which CAV9 infects efficiently by an RGD-dependent mechanism. Significantly, this infection is blocked by an antibody to α
v
β
6
, while this antibody did not block the low level of infection by the RGD-less mutant. Thus, integrin α
v
β
6
is an RGD-dependent receptor for CAV9 and may be important in natural CAV9 infections.
The VP7 Outer Capsid Protein of Rotavirus Induces Polyclonal B-Cell Activation
Authors: Blutt Sarah E. , Crawford Sue E. , Warfield Kelly L. , Lewis Dorothy E. , Estes Mary K. , Conner Margaret E. 
Published: June 2004

ABSTRACTThe early response to a homologous rotavirus infection in mice includes a T-cell-independent increase in the number of activated B lymphocytes in the Peyer's patches. The mechanism of this activation has not been previously determined. Since rotavirus has a repetitively arranged triple-layered capsid and repetitively arranged antigens can induce activation of B cells, one or more of the capsid proteins could be responsible for the initial activation of B cells during infection. To address this question, we assessed the ability of rotavirus and virus-like particles to induce B-cell activation in vivo and in vitro. Using infectious rotavirus, inactivated rotavirus, noninfectious but replication-competent virus, and virus-like particles, we determined that neither infectivity nor RNA was necessary for B-cell activation but the presence of the rotavirus outer capsid protein, VP7, was sufficient for murine B-cell activation. Preincubation of the virus with neutralizing VP7 antibodies inhibited B-cell activation. Polymyxin B treatment and boiling of the virus preparation were performed, which ruled out possible lipopolysaccharide contamination as the source of activation and confirmed that the structural conformation of VP7 is important for B-cell activation. These findings indicate that the structure and conformation of the outer capsid protein, VP7, initiate intestinal B-cell activation during rotavirus infection.