bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variations in the matrix metalloproteinase‐1 promoter and risk of susceptibility and/or severity of chronic periodontitis in the Czech population
Authors: Izakovičová Hollá L. , Jurajda M. , Fassmann A. , Dvorakova N. , Znojil V. , Vacha J. 
Published: July 2004

AbstractObjectives: Matrix metalloproteinase‐1 (MMP‐1) is a potent enzyme degrading extracellular matrix that was implicated in the pathogenesis of chronic periodontitis. Therefore, the aim of our study was to examine the association between three promoter polymorphisms of the MMP‐1 gene and chronic periodontitis susceptibility and/or severity in a Czech population.Materials and Methods: A total of 329 Caucasian subjects were enrolled in this study. They were 133 patients with mild to severe chronic periodontitis and 196 unrelated control subjects. MMP‐1 promoter polymorphisms (−1607 1G/2G, −519A/G, and −422A/T) were genotyped using standard polymerase chain reaction–restriction fragment length product methods.Results: Genotype analysis of the three single nucleotide polymorphisms across 27 different combinations showed significant association with chronic periodontitis (p<0.05). Analyses of individual polymorphisms showed no differences in distribution of the −519A/G and −422A/T variants between periodontitis and control groups. However, a trend to increased frequency of the −1607 1G allele was observed in patients with chronic periodontitis compared with the controls (p=0.054). When the groups were further stratified by smoking status, the 1G allele was associated with chronic periodontitis among non‐smokers but not among smokers (p=0.033). On the contrary, the distribution of genotype frequencies of the MMP‐1 −422A/T polymorphism was different between the patient and control smokers with respect to heterozygotes (73.91% versus 50.91%; p=0.017).Conclusions: Our results demonstrate that the polymorphisms in the MMP‐1 promoter may have only a small effect on the etiopathogenesis of chronic periodontitis.
A longitudinal study of the relationship between periodontal disease and bone mineral density in community‐dwelling older adults
Authors: Yoshihara Akihiro , Seida Yoshikazu , Hanada Nobuhiro , Miyazaki Hideo 
Published: July 2004

AbstractObjective: Bone loss is a common feature of periodontitis and osteoporosis. Both diseases may share common etiologic agents which may either affect or modulate the process of both diseases. The purpose of this study was to evaluate the relationship between systemic bone mineral density (BMD) and periodontal disease among older people.Materials and Methods: Among all 4542 inhabitants aged 70 years according to a registry of residents in Niigata city in Japan, 600 people were selected randomly. One hundred and eighty‐four subjects who did not have diabetes mellitus, whose blood sugar was <140 mg/dl, who had more than 20 teeth, who were non‐smokers, and who did not take medication for osteoporosis, were included in the study. Four dentists performed clinical evaluations on probing attachment level (PAL). We also utilized the data on BMD of the heel, which we measured using an ultrasound bone densitometer. Follow‐up clinical surveys were done by measuring PAL after 3 years. Finally, 179 subjects who could participate in both the baseline and the follow‐up examinations were included in the analysis. After dividing the subjects into an osteopenia group (OG) and non‐osteopenia group (NOG), we evaluated the relationship between BMD and the number of progressive sites which had 3 mm additional attachment loss during 3 years after controlling the known confounding factors.Results: The mean number of progressive sites for the OG and the NOG, respectively, were 4.65±5.51 and 3.26±3.01 in females and 6.88±9.41 and 3.41±2.79 in males. Two‐way analysis of variance was performed to discriminate among effects of gender, BMD, and gender–BMD interaction. A significant effect of BMD (OG or NOG, p=0.043) with a significant interaction (p=0.038) was observed. Furthermore, BMD was associated with the number of progressive sites which had 3 mm additional attachment loss during the 3 years (p=0.001) by multiple linear regression analysis.Conclusions: This study suggested that there was a significant relationship between periodontal disease and general BMD.
The electric toothbrush: analysis of filaments under stereomicroscope
Authors: Checchi L. , Farina E. , Felice P. , Montevecchi M. 
Published: July 2004

AbstractBackground: The use of manual and electric toothbrushes has a fundamental role in primary prevention in oral hygiene. However, aggressive use of the toothbrush, especially those with non‐rounded filaments, can result in lesions in both soft and hard oral tissue. Without doubt, the electric toothbrush is a useful aid for the patient, and it is therefore interesting to evaluate not only its effectiveness in plaque removal, but also the relationship between morphology of filaments and incidence of muco‐gingival pathologies.Objective: The aim of this research was to evaluate various forms of bristles of electric toothbrushes under a stereomicroscope vision.Data sources: Brushes tested included two samples of toothbrushes from six different types. Tufts from the same position on the toothbrush head were removed and examined under stereomicroscope. In this study the percentage of rounded filaments that is considered acceptable and non‐traumatic was evaluated according to the Silverstone and Featherstone classification.Conclusions: Morphological analysis of electric toothbrush filaments revealed a low percentage of rounded filaments. In only four of 12 electric toothbrushes tested there were more than 50% of the filaments rounded in appearance.
Adeno-Associated Virus Site-Specific Integration and AAVS1 Disruption
Authors: Hamilton Henry , Gomos Janette , Berns Kenneth I. , Falck-Pedersen Erik 
Published: July 2004

ABSTRACT
Adeno-associated virus (AAV) is a single-stranded DNA virus with a unique biphasic lifestyle consisting of both a productive and a latent phase. Typically, the productive phase requires coinfection with a helper virus, for instance adenovirus, while the latent phase dominates in healthy cells. In the latent state, AAV is found integrated site specifically into the host genome at chromosome 19q13.4 qtr (AAVS1), the only animal virus known to integrate in a defined location. In this study we investigated the latent phase of serotype 2 AAV, focusing on three areas: AAV infection, rescue, and integration efficiency as a function of viral multiplicity of infection (MOI); efficiency of site-specific integration; and disruption of the AAVS1 locus. As expected, increasing the AAV MOI resulted in an increase in the percentage of cells infected, with 80% of cells infected at an MOI of 10. Additional MOI only marginally effected a further increase in percentage of infected cells. In contrast to infection, we found very low levels of integration at MOIs of less than 10. At an MOI of 10, at which 80% of cells are infected, less than 5% of clonal cell lines contained integrated AAV DNA. At an MOI of 100 or greater, however, 35 to 40% of clonal cell lines contained integrated AAV DNA. Integration and the ability to rescue viral genomes were highly correlated. Analysis of integrated AAV indicated that essentially all integrants were AAVS1 site specific. Although maximal integration efficiency approached 40% of clonal cell lines (essentially 50% of infected cells), over 80% of cell lines contained a genomic disruption at the AAVS1 integration locus on chromosome 19 (≈100% of infected cells). Rep expression by itself and in the presence of a plasmid integration substrate was able to mediate this disruption of the AAVS1 site. We further characterized the disruption event and demonstrated that it resulted in amplification of the AAVS1 locus. The data are consistent with a revised model of AAV integration that includes preliminary expansion of a defined region in AAVS1.
Compartmentalization of Human Immunodeficiency Virus Type 1 between Blood Monocytes and CD4+T Cells during Infection
Authors: Fulcher Jennifer A. , Hwangbo Yon , Zioni Rafael , Nickle David , Lin Xudong , Heath Laura , Mullins James I. , Corey Lawrence , Zhu Tuofu 
Published: July 2004

ABSTRACTDistinct sequences of human immunodeficiency virus type 1 (HIV-1) have been found between different tissue compartments or subcompartments within a given tissue. Whether such compartmentalization of HIV-1 occurs between different cell populations is still unknown. Here we address this issue by comparing HIV-1 sequences in the second constant region through the fifth hypervariable region (C2 to V5) of the surface envelope glycoprotein (Env) between viruses in purified blood CD14+monocytes and CD4+T cells obtained longitudinally from five infected patients over a time period ranging from 117 to 3,409 days postseroconversion. Viral populations in both cell types at early infection time points appeared relatively homogeneous. However, later in infections, all five patients showed heterogeneous populations in both CD14+monocytes and CD4+T cells. Three of the five patients had CD14+monocyte populations with significantly more genetic diversity than the CD4+T-cell population, while the other two patients had more genetic diversity in CD4+T cells. The cellular compartmentalization of HIV-1 between CD14+monocytes and CD4+T cells was not seen early during infections but was evident at the later time points for all five patients, indicating an association of viral compartmentalization with the time course of HIV-1 infection. The majority of HIV-1 V3 sequences indicated a macrophage-tropic phenotype, while a V3 sequence-predicted T-cell tropic virus was found in the CD4+T cells and CD14+monocytes of two patients. These findings suggest that HIV-1 in CD14+monocytes could disseminate and evolve independently from that in CD4+T cells over the course of HIV-1 infection, which may have implications on the development of new therapeutic strategies.
Canine Distemper Virus and Measles Virus Fusion Glycoprotein Trimers: Partial Membrane-Proximal Ectodomain Cleavage Enhances Function
Authors: von Messling Veronika , Milosevic Dragana , Devaux Patricia , Cattaneo Roberto 
Published: July 2004

ABSTRACT

The trimeric fusion (F) glycoproteins of morbilliviruses are activated by furin cleavage of the precursor F
0
into the F
1
and F
2
subunits. Here we show that an additional membrane-proximal cleavage occurs and modulates F protein function. We initially observed that the ectodomain of approximately one in three measles virus (MV) F proteins is cleaved proximal to the membrane. Processing occurs after cleavage activation of the precursor F
0
into the F
1
and F
2
subunits, producing F
1a
and F
1b
fragments that are incorporated in viral particles. We also detected the F
1b
fragment, including the transmembrane domain and cytoplasmic tail, in cells expressing the canine distemper virus (CDV) or mumps virus F protein. Six membrane-proximal amino acids are necessary for efficient CDV F
1a/b
cleavage. These six amino acids can be exchanged with the corresponding MV F protein residues of different sequence without compromising function. Thus, structural elements of different sequence are functionally exchangeable. Finally, we showed that the alteration of a block of membrane-proximal amino acids results in diminished fusion activity in the context of a recombinant CDV. We envisage that selective loss of the membrane anchor in the external subunits of circularly arranged F protein trimers may disengage them from pulling the membrane centrifugally, thereby facilitating fusion pore formation.
A Mouse-Adapted Enterovirus 71 Strain Causes Neurological Disease in Mice after Oral Infection
Authors: Wang Ya-Fang , Chou Chun-Ting , Lei Huan-Yao , Liu Ching-Chuan , Wang Shih-Min , Yan Jing-Jou , Su Ih-Jen , Wang Jen-Reng , Yeh Trai-Ming , Chen Shun-Hua , Yu Chun-Keung 
Published: July 2004

ABSTRACT

A mouse-adapted enterovirus 71 (EV71) strain with increased virulence in mice, MP4, was generated after four serial passages of the parental EV71 strain 4643 in mice. Strain MP4 exhibited a larger plaque size, grew more rapidly, and was more cytotoxic in vitro than strain 4643. Although strains 4643 and MP4 both induced apoptosis of SK-N-SH human neuroblastoma cells, MP4 was more virulent than 4643 in 1-day-old mice (50% lethal doses, 10
2
and 10
4
PFU/mouse, respectively). Strain MP4 (5 × 10
6
PFU/mouse), but not 4643, could orally infect 7-day-old mice, resulting in rear-limb paralysis followed by death 5 to 9 days after inoculation with the virus. Histopathologically, neuronal loss and apoptosis were evident in the spinal cords as well as the brain stems of the infected mice. The limb muscles displayed massive necrosis. There was early and transient virus replication in the intestines, whereas the spinal cord, brain, and muscle became the sites of viral replication during the late phase of the infection. Virus transmission occurred among infected and noninfected cagemates, as demonstrated by the occurrence of seroconversion and the presence of viable viruses in the stool samples of the latter. Protection against EV71 challenge was demonstrated following administration of hyperimmune serum 1 day after inoculation with the virus. Nucleotide sequence analysis of the genome of EV71 strain MP4 revealed four nucleotide changes on the 5′ untranslated region, three on the VP2 region, and eight on the 2C region, resulting in one and four amino acid substitutions in the VP2 and 2C proteins, respectively.
Inhibition of Infectious Pancreatic Necrosis Virus Replication by Atlantic Salmon Mx1 Protein
Authors: Larsen Rannveig , Røkenes Torunn P. , Robertsen Børre 
Published: July 2004

ABSTRACT
Mx proteins form a family of interferon (IFN)-induced GTPases with potent antiviral activity against various single-stranded RNA viruses in mammals and chickens. In fish, alpha/beta IFN has been reported to inhibit the replication of infectious pancreatic necrosis virus (IPNV), but the mode of action has not been elucidated. A correlation between the inhibition of IPNV and Mx protein expression has, however, been observed. To examine whether Atlantic salmon Mx1 protein (ASMx1) possesses antiviral activity against IPNV, CHSE-214 cells constitutively expressing ASMx1 were established. ASMx1 appeared to be localized in the cytoplasm. The ASMx1-expressing clone selected showed a severely reduced IPNV-induced cytopathic effect, which was confirmed by a 500-fold reduction in virus yield. The antiviral activity against IPNV was further confirmed by the inhibition of virus protein synthesis and the reduced accumulation of virus transcripts. The present work further adds to the body of evidence which suggests that antiviral activity is a major functional role of vertebrate Mx proteins. Moreover, the list of viruses inhibited by Mx proteins is extended to include double-stranded RNA viruses.
Comprehensive Mutational Analysis of a Herpesvirus Gene in the Viral Genome Context Reveals a Region Essential for Virus Replication
Authors: Bubeck Anja , Wagner Markus , Ruzsics Zsolt , Lötzerich Mark , Iglesias Margot , Singh Ila R. , Koszinowski Ulrich H. 
Published: July 2004

ABSTRACT

Essential viral proteins perform vital functions during morphogenesis via a complex interaction with other viral and cellular gene products. Here, we present a novel approach to comprehensive mutagenesis of essential cytomegalovirus genes and biological analysis in the 230-kbp-genome context. A random Tn
7
-based mutagenesis procedure at the single-gene level was combined with site-specific recombination via the FLP/FLP recognition target site system for viral genome reconstitution. We show the function of more than 100 mutants from a larger library of M50/p35, a protein involved in capsid egress from the nucleus. This protein recruits other viral proteins and cellular enzymes to the inner nuclear membrane. Our approach enabled us to rapidly discriminate between essential and nonessential regions within the coding sequence. Based on the prediction of the screen, we were able to map a site essential for viral protein-protein interaction at the amino acid level.
Herpes Simplex Virus Type 1 Infection Induces the Stabilization of p53 in a USP7- and ATM-Independent Manner
Authors: Boutell Chris , Everett Roger D. 
Published: July 2004

ABSTRACT

The major oncoprotein p53 regulates several cellular antiproliferation pathways that can be triggered in response to a variety of cellular stresses, including viral infection. The stabilization of p53 is a key factor in the ability of cells to initiate an efficient transcriptional response after cellular stress. Here we present data demonstrating that herpes simplex virus type 1 (HSV-1) infection of HFFF-2 cells, a low-passage-number nontransformed human primary cell line, results in the stabilization of p53. This process required viral immediate-early gene expression but occurred independently of the viral regulatory protein ICP0 and viral DNA replication. No specific viral protein could be identified as being solely responsible for the effect, which appears to be a cellular response to developing HSV-1 infections. HSV-1 infection also induced the phosphorylation of p53 at residues Ser15 and Ser20, which have previously been implicated in its stabilization in response to DNA damage. However, an HSV-1 infection of ATM
−/−
cells, which lack a kinase implicated in these phosphorylation events, did not lead to the phosphorylation of p53 at these residues, but nonetheless p53 was stabilized. We also show that the wild-type p53 expressed by osteosarcoma U2OS cells can be stabilized in response to DNA damage induced by UV irradiation, but not in response to HSV-1 infection. These data suggest that multiple cellular mechanisms are initiated to stabilize p53 during an HSV-1 infection. These mechanisms occur independently of ICP0 and its ability to sequester USP7 and may differ from those initiated in response to DNA damage.
Porcine Arterivirus Infection of Alveolar Macrophages Is Mediated by Sialic Acid on the Virus
Authors: Delputte Peter L. , Nauwynck Hans J. 
Published: July 2004

ABSTRACTRecently, we showed that porcine sialoadhesin (pSn) mediates internalization of the arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) in alveolar macrophages (Vanderheijden et al., J. Virol. 77:8207-8215, 2003). In rodents and humans, sialoadhesin, or Siglec-1, has been described as a macrophage-restricted molecule and to specifically bind sialic acid moieties. In the current study, we investigated whether pSn is a sialic acid binding protein and, whether so, whether this property is important for its function as a PRRSV receptor. Using untreated and neuraminidase-treated sheep erythrocytes, we showed that pSn binds sialic acid. Furthermore, pSn-specific monoclonal antibody 41D3, which blocks PRRSV infection, inhibited this interaction. PRRSV attachment to and infection of porcine alveolar macrophages (PAM) were both shown to be dependent on the presence of sialic acid on the virus: neuraminidase treatment of virus but not of PAM blocked infection and reduced attachment. Enzymatic removal of all N-linked glycans on the virus with N-glycosidase F reduced PRRSV infection, while exclusive removal of nonsialylated N-linked glycans of the high-mannose type with endoglycosidase H had no significant effect. Free sialyllactose and sialic acid containing (neo)glycoproteins reduced infection, while lactose and (neo)glycoproteins devoid of sialic acids had no significant effect. Studies with linkage-specific neuraminidases and lectins indicated that α2-3- and α2-6-linked sialic acids on the virion are important for PRRSV infection of PAM. From these results, we conclude that pSn is a sialic acid binding lectin and that interactions between sialic acid on the PRRS virion and pSn are essential for PRRSV infection of PAM.
Regulation of Relative Abundance of Arterivirus Subgenomic mRNAs
Authors: Pasternak Alexander O. , Spaan Willy J. M. , Snijder Eric J. 
Published: July 2004

ABSTRACT

The subgenomic (sg) mRNAs of arteriviruses (order
Nidovirales
) form a 5′- and 3′-coterminal nested set with the viral genome. Their 5′ common leader sequence is derived from the genomic 5′-proximal region. Fusion of sg RNA leader and “body” segments involves a discontinuous transcription step. Presumably during minus-strand synthesis, the nascent RNA strand is transferred from one site in the genomic template to another, a process guided by conserved transcription-regulating sequences (TRSs) at these template sites. Subgenomic RNA species are produced in different but constant molar ratios, with the smallest RNAs usually being most abundant. Factors thought to influence sg RNA synthesis are size differences between sg RNA species, differences in sequence context between body TRSs, and the mutual influence (or competition) between strand transfer reactions occurring at different body TRSs. Using an
Equine arteritis virus
infectious cDNA clone, we investigated how body TRS activity affected sg RNA synthesis from neighboring body TRSs. Flanking sequences were standardized by head-to-tail insertion of several copies of an RNA7 body TRS cassette. A perfect gradient of sg RNA abundance, progressively favoring smaller RNA species, was observed. Disruption of body TRS function by mutagenesis did not have a significant effect on the activity of other TRSs. However, deletion of body TRS-containing regions enhanced synthesis of sg RNAs from upstream TRSs but not of those produced from downstream TRSs. The results of this study provide considerable support for the proposed discontinuous extension of minus-strand RNA synthesis as a crucial step in sg RNA synthesis.
Human Immunodeficiency Virus Type 1 Infection Induces Cyclin T1 Expression in Macrophages
Authors: Liou Li-Ying , Herrmann Christine H. , Rice Andrew P. 
Published: July 2004

ABSTRACTThe Tat protein of human immunodeficiency virus type 1 (HIV-1) is essential for viral replication and activates RNA polymerase II transcriptional elongation through the association with a cellular protein kinase composed of Cdk9 and cyclin T1. Tat binds to this kinase complex through a direct protein-protein interaction with cyclin T1. Monocytes/macrophages are important targets of HIV-1 infection, and previous work has shown that cyclin T1 but not Cdk9 protein expression is low in monocytes isolated from blood. While Cdk9 expression is expressed at a high level during monocyte differentiation to macrophages in vitro, cyclin T1 expression is induced during the first few days of differentiation and is shut off after 1 to 2 weeks. We show here that the shutoff of cyclin T1 expression in late-differentiated macrophages involves proteasome-mediated proteolysis. We also show that cyclin T1 can be reinduced by a number of pathogen-associated molecular patterns that activate macrophages, indicating that up-regulation of cyclin T1 is part of an innate immune response. Furthermore, we found that HIV-1 infection early in macrophage differentiation results in sustained cyclin T1 expression, while infection at late times in differentiation results in the reinduction of cyclin T1. Expression of the viral Nef protein from an adenovirus vector suggests that Nef contributes to the HIV-1 induction of cyclin T1. These findings suggest that HIV-1 infection hijacks a component of the innate immune response in macrophages that results in enhancement rather than inhibition of viral replication.