bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Associated with Differences between Conventional Contact Tracing and Molecular Epidemiology in Study of Tuberculosis Transmission and Analysis in the City of Barcelona, Spain
Authors: Borrell Sònia , Español Montserrat , Orcau Àngels , Tudó Griselda , March Francesca , Caylà Joan A. , Jansà Josep Maria , Alcaide Fernando , Martín-Casabona Núria , Salvadó Margarita , Martínez José Antonio , Vidal Rafael , Sánchez Francesca , Altet Neus , Coll Pere , González-Martín Juliàn 
Published: November 2008

ABSTRACTThe aim of this study was to analyze the factors associated with conventional contact tracing (CCT) and molecular epidemiology (ME) methods in assessing tuberculosis (TB) transmission, comparing the populations studied and the epidemiological links established by both methods. Data were obtained from TB case and CCT registries, and ME was performed using IS6110-based restriction fragment length polymorphism (RFLP) analysis and mycobacterial interspersed repetitive unit 12 (MIRU12) typing as a secondary typing method. During two years (2003 and 2004), 892 cases of TB were reported, of which 687 (77%) were confirmed by culture. RFLP analysis was performed with 463 (67.4%) of the 687 isolated strains, and MIRU12 types in 75 strains were evaluated; 280 strains (60.5%) had a unique RFLP pattern, and 183 (39.5%) shared patterns, grouping into 65 clusters. CCT of 613 (68.7%) of 892 cases detected 44 clusters involving 101 patients. The results of both CCT and ME methods yielded 96 clusters involving 255 patients. The household link was the one most frequently identified by CCT (corresponding to 80.7% of the cases clustered by this method), whereas nonhousehold and unknown links were associated with 94.1% of the strains clustered by ME. When both methods were used in 351 cases (39.3%), they showed the same results in 214 cases (61%). Of the remainder, 106 (30.2%) were clustered only by ME, 19 (5.5%) were clustered only by CCT, and 12 (3.4%) were clustered by both methods but into different clusters. Patients with factors potentially associated with social problems were less frequently studied by CCT (P= 0.002), whereas patients of <15 years of age, most with negative cultures, were less frequently studied by ME (P= 0.005). Significant differences in the populations studied by ME versus CCT were observed, possibly explaining the scarce correlation found between the results of these methods. Moreover, ME allowed the detection of nonhousehold contact relationships, whereas CCT was more useful for tracing transmission chains involving patients of <15 years of age. In conclusion, the two methods are complementary, suggesting the need to improve the methodology of contact study protocols.
Borrelia carolinensissp. nov., a New (14th) Member of theBorrelia burgdorferiSensu Lato Complex from the Southeastern Region of the United States
Authors: Rudenko Nataliia , Golovchenko Maryna , Grubhoffer Libor , Oliver James H. 
Published: November 2008

ABSTRACTApproximately 118Borreliaisolates were cultured from a variety of rodents, birds, and ticks collected in the southern United States. In addition to a highly diverse group ofBorrelia bissettiistrains and a homogenous group ofBorrelia burgdorferisensu stricto strains, a group of 16 isolates with unusual characteristics was found. The isolates were cultured from ear biopsy samples of the rodentsPeromyscus gossypinusandNeotoma floridanatrapped at five localities in South Carolina. A multilocus sequence analysis of therrf-rrlintergenic spacer, 16S rRNA,fla,ospA, andp66genes were used to clarify the taxonomic status of the new group ofB. burgdorferisensu lato isolates. Thirteen species of theB. burgdorferisensu lato complex were used as controls. Unique restriction fragment length polymorphism patterns of therrf-rrlintergenic spacer region andflagene were recognized. Unique signature nucleotides were also found in the 16S rRNA gene. A phylogenetic analysis shows that the 16 new isolates cluster together but separately from the other species in theB. burgdorferisensu lato complex. Our data strongly support the recognition of the 16 isolates as a newB. burgdorferisensu lato species. We propose to name this genospecies “Borrelia carolinensis” with respect to the place of its currently known geographic location.
Single-Nucleotide Polymorphisms in Rv2629 Are Specific for
Mycobacterium tuberculosis
Genotypes Beijing and Ghana but Not Associated with Rifampin Resistance
Authors: Homolka Susanne , Köser Claudio , Archer John , Rüsch-Gerdes Sabine , Niemann Stefan 
Published: November 2008

ABSTRACT

Sequence analysis of 58 multidrug-resistant
Mycobacterium tuberculosis
complex strains from Germany and 55 susceptible strains from a reference collection comprising major phylogenetic lineages confirmed that variations in Rv2629, 191A/C and 965C/T, are specific for genotypes Beijing and Ghana, respectively, but not involved in the development of rifampin (rifampicin) resistance.
Acute Respiratory Failure Involving an R Variant of
Mycobacterium abscessus
Authors: Catherinot Emilie , Roux Anne-Laure , Macheras Edouard , Hubert Dominique , Matmar Moussa , Dannhoffer Luc , Chinet Thierry , Morand Philippe , Poyart Claire , Heym Beate , Rottman Martin , Gaillard Jean-Louis , Herrmann Jean-Louis 
Published: November 2008

ABSTRACT

We report the case of a cystic fibrosis patient colonized with a smooth-morphotype form of
Mycobacterium abscessus
who developed acute respiratory failure with the emergence of an isogenic rough (R) variant while he was recovering from peritonitis-induced shock. This report emphasizes the role of R forms in severe
M. abscessus
infections.
Comparison of Cefoxitin and Oxacillin Disk Diffusion Methods for Detection of
mecA
-Mediated Resistance in
Staphylococcus aureus
in a Large-Scale Study
Authors: Broekema Nicole M. , Van Tam T. , Monson Timothy A. , Marshall Steven A. , Warshauer David M. 
Published: November 2008

ABSTRACT

The recommended breakpoints for the cefoxitin disk diffusion test for
Staphylococcus aureus
were recently modified. In this large-sample study, cefoxitin sensitivity and specificity compared to those of oxacillin were 97.3% and 100%, respectively. This study validated the new cefoxitin breakpoints for the detection of
mecA
-mediated resistance in
S. aureus
.
Development of an Oligonucleotide Array for Direct Detection of Fungi in Sputum Samples from Patients with Cystic Fibrosis
Authors: Bouchara Jean-Phillippe , Hsieh Hsin Yi , Croquefer Sabine , Barton Richard , Marchais Veronique , Pihet Marc , Chang Tsung Chain 
Published: November 2008

ABSTRACT
Cystic fibrosis (CF) is the most common inherited genetic disease in Caucasian populations. Besides bacteria, many species of fungi may colonize the respiratory tract of these patients, sometimes leading to true respiratory infections. In this study, an oligonucleotide array capable of identifying 20 fungal species was developed to directly detect fungi in the sputum samples of CF patients. Species-specific oligonucleotide probes were designed from the internal transcribed spacer (ITS) regions of the rRNA operon and immobilized on a nylon membrane. The fungal ITS regions were amplified by PCR and hybridized to the array for species identification. The array was validated by testing 182 target strains (strains which we aimed to identify) and 141 nontarget strains (135 species), and a sensitivity of 100% and a specificity of 99.2% were obtained. The validated array was then used for direct detection of fungi in 57 sputum samples from 39 CF patients, and the results were compared to those obtained by culture. For 16 sputum samples, the results obtained by the array corresponded with those obtained by culture. For 33 samples, the array detected more fungal species than culture did, while the reverse was found for eight samples. The accuracy of the array for fungal detection in sputum samples was confirmed (or partially confirmed) in some samples by cloning and resequencing the amplified ITS fragments. The present array is a useful tool for both the simultaneous detection of multiple fungal species present in the sputa of CF patients and the identification of fungi isolated from these patients.
Presence of the KPC Carbapenemase Gene in
Enterobacteriaceae
Causing Bacteremia and Its Correlation with In Vitro Carbapenem Susceptibility
Authors: Marschall Jonas , Tibbetts Robert J. , Dunne W. Michael , Frye Jonathan G. , Fraser Victoria J. , Warren David K. 
Published: November 2008

ABSTRACT

During 6 months, we obtained
Enterobacteriaceae
isolates from patients with gram-negative bacteremia at a 1,250-bed teaching hospital in St. Louis, MO, and compared carbapenem susceptibilities with the presence of
bla
KPC
, a transferable carbapenemase gene. Three (1.2%) out of 243 isolates were
bla
KPC
positive. Ertapenem nonsusceptibility had a low positive predictive value.
Respiratory Syncytial Virus Activates Innate Immunity through Toll-Like Receptor 2
Authors: Murawski Matthew R. , Bowen Glennice N. , Cerny Anna M. , Anderson Larry J. , Haynes Lia M. , Tripp Ralph A. , Kurt-Jones Evelyn A. , Finberg Robert W. 
Published: November 2008

ABSTRACTRespiratory syncytial virus (RSV) is a common cause of infection that is associated with a range of respiratory illnesses, from common cold-like symptoms to serious lower respiratory tract illnesses such as pneumonia and bronchiolitis. RSV is the single most important cause of serious lower respiratory tract illness in children <1 year of age. Host innate and acquired immune responses activated following RSV infection have been suspected to contribute to RSV disease. Toll-like receptors (TLRs) activate innate and acquired immunity and are candidates for playing key roles in the host immune response to RSV. Leukocytes express TLRs, including TLR2, TLR6, TLR3, TLR4, and TLR7, that can interact with RSV and promote immune responses following infection. Using knockout mice, we have demonstrated that TLR2 and TLR6 signaling in leukocytes can activate innate immunity against RSV by promoting tumor necrosis factor alpha, interleukin-6, CCL2 (monocyte chemoattractant protein 1), and CCL5 (RANTES). As previously noted, TLR4 also contributes to cytokine activation (L. M. Haynes, D. D. Moore, E. A. Kurt-Jones, R. W. Finberg, L. J. Anderson, and R. A. Tripp, J. Virol. 75:10730-10737, 2001, and E. A. Kurt-Jones, L. Popova, L. Kwinn, L. M. Haynes, L. P. Jones, R. A. Tripp, E. E. Walsh, M. W. Freeman, D. T. Golenbock, L. J. Anderson, and R. W. Finberg, Nat. Immunol. 1:398-401, 2000). Furthermore, we demonstrated that signals generated following TLR2 and TLR6 activation were important for controlling viral replication in vivo. Additionally, TLR2 interactions with RSV promoted neutrophil migration and dendritic cell activation within the lung. Collectively, these studies indicate that TLR2 is involved in RSV recognition and subsequent innate immune activation.
Hantaan Virus Nucleocapsid Protein Binds to Importin α Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced Activation of Nuclear Factor Kappa B
Authors: Taylor Shannon L. , Frias-Staheli Natalia , García-Sastre Adolfo , Schmaljohn Connie S. 
Published: November 2008

ABSTRACT
Hantaviruses such as Hantaan virus (HTNV) and Andes virus cause two human diseases, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, respectively. For both, disease pathogenesis is thought to be immunologically mediated and there have been numerous reports of patients with elevated levels of proinflammatory and inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), in their sera. Multiple viruses have developed evasion strategies to circumvent the host cell inflammatory process, with one of the most prevalent being the disruption of nuclear factor kappa B (NF-κB) activation. We hypothesized that hantaviruses might also moderate host inflammation by interfering with this pathway. We report here that the nucleocapsid (N) protein of HTNV was able to inhibit TNF-α-induced activation of NF-κB, as measured by a reporter assay, and the activation of endogenous p65, an NF-κB subunit. Surprisingly, there was no defect in the degradation of the inhibitor of NF-κB (IκB) protein, nor was there any alteration in the level of p65 expression in HTNV N-expressing cells. However, immunofluorescence antibody staining demonstrated that cells expressing HTNV N protein and a green fluorescent protein-p65 fusion had limited p65 nuclear translocation. Furthermore, we were able to detect an interaction between HTNV N protein and importin α, a nuclear import molecule responsible for shuttling NF-κB to the nucleus. Collectively, our data suggest that HTNV N protein can sequester NF-κB in the cytoplasm, thus inhibiting NF-κB activity. These findings, which were obtained using cells transfected with cDNA representing the HTNV N gene, were confirmed using HTNV-infected cells.
Engagement of the CD4 Receptor Affects the Redistribution of Lck to the Immunological Synapse in Primary T Cells: Implications for T-Cell Activation during Human Immunodeficiency Virus Type 1 Infection
Authors: Nyakeriga Alice M. , Fichtenbaum Carl J. , Goebel Jens , Nicolaou Stella A. , Conforti Laura , Chougnet Claire A. 
Published: November 2008

ABSTRACTUnderstanding the molecular mechanisms underlying dysregulated immune responses in human immunodeficiency virus type 1 (HIV-1) infection is crucial for the control of HIV/AIDS. Despite the postulate that HIV envelope glycoprotein gp120-CD4 interactions lead to impaired T-cell responses, the precise mechanisms underlying such association are not clear. To address this, we analyzed Lck and F-actin redistribution into the immunological synapse in stimulated human primary CD4+T cells from HIV-1-infected donors. Similar experiments were performed with CD4+T cells from HIV-uninfected donors, which were exposed to anti-CD4 domain 1 antibodies, as an in vitro model of gp120-CD4 interactions, or aldithriol-inactivated HIV-1 virions before stimulation. CD4+T cells from HIV-infected patients exhibited a two- to threefold inhibition of both Lck and F-actin recruitment into the synapse, compared to cells from uninfected donors. Interestingly, defective recruitment of Lck was ameliorated following suppressive highly active antiretroviral therapy. Engagement of the CD4 receptor on T cells from HIV-uninfected donors before anti-CD3/CD28 stimulation led to similar defects. Furthermore, the redistribution of Lck into lipid rafts was abrogated by CD4 preengagement. Our results suggest that the engagement of CD4 by HIV gp120 prior to T-cell receptor stimulation leads to dysregulation of early signaling events and could consequently play an important role in impaired CD4+T-cell function.
mRNA Translation Regulation by the Gly-Ala Repeat of Epstein-Barr Virus Nuclear Antigen 1
Authors: Apcher Sebastien , Komarova Anastassia , Daskalogianni Chrysoula , Yin Yili , Malbert-Colas Laurence , Fåhraeus Robin 
Published: November 2008

ABSTRACTThe glycine-alanine repeat (GAr) sequence of the Epstein-Barr virus-encoded EBNA-1 prevents presentation of antigenic peptides to major histocompatibility complex class I molecules. This has been attributed to its capacity to suppress mRNA translation incis. However, the underlying mechanism of this function remains largely unknown. Here, we have further investigated the effect of the GAr as a regulator of mRNA translation. Introduction of silent mutations in each codon of a 30-amino-acid GAr sequence does not significantly affect the translation-inhibitory capacity, whereas minimal alterations in the amino acid composition have strong effects, which underscores the observation that the amino acid sequence and not the mRNA sequence mediates GAr-dependent translation suppression. The capacity of the GAr to repress translation is dose and position dependent and leads to a relative accumulation of preinitiation complexes on the mRNA. Taken together with the surprising observation that fusion of the 5′ untranslated region (UTR) of the c-myc mRNA to the 5′ UTR of GAr-carrying mRNAs specifically inactivates the effect of the GAr, these results indicate that the GAr targets components of the translation initiation process. We propose a model in which the nascent GAr peptide delays the assembly of the initiation complex on its own mRNA.
HLA-Associated Clinical Progression Correlates with Epitope Reversion Rates in Early Human Immunodeficiency Virus Infection
Authors: Duda A. , Lee-Turner L. , Fox J. , Robinson N. , Dustan S. , Kaye S. , Fryer H. , Carrington M. , McClure M. , Mclean A. R. , Fidler S. , Weber J. , Phillips R. E. , Frater A. J. 
Published: November 2008

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) can evade immunity shortly after transmission to a new host but the clinical significance of this early viral adaptation in HIV infection is not clear. We present an analysis of sequence variation from a longitudinal cohort study of HIV adaptation in 189 acute seroconverters followed for up to 3 years. We measured the rates of variation within well-defined epitopes to determine associations with the HLA-linked hazard of disease progression. We found early reversion across both thegagandpolgenes, with a 10-fold faster rate of escape ingag(2.2 versus 0.27 forward mutations/1,000 amino acid sites). For most epitopes (23/34), variation in the HLA-matched and HLA-unmatched controls was similar. For a minority of epitopes (8/34, and generally associated with HLA class I alleles that confer clinical benefit), new variants appeared early and consistently over the first 3 years of infection. Reversion occurred early at a rate which was HLA-dependent and correlated with the HLA class 1-associated relative hazard of disease progression and death (P= 0.0008), reinforcing the association between strong cytotoxic T-lymphocyte responses, viral fitness, and disease status. These data provide a comprehensive overview of viral adaptation in the first 3 years of infection. Our findings of HLA-dependent reversion suggest that costs are borne by some escape variants which may benefit the host, a finding contrary to a simple immune evasion paradigm. These epitopes, which are both strongly and frequently recognized, and for which escape involves a high cost to the virus, have the potential to optimize vaccine design.
Specific Inhibition of the PKR-Mediated Antiviral Response by the Murine Cytomegalovirus Proteins m142 and m143
Authors: Budt Matthias , Niederstadt Lars , Valchanova Ralitsa S. , Jonjić Stipan , Brune Wolfram 
Published: November 2008

ABSTRACTDouble-stranded RNA (dsRNA) produced during viral infection activates several cellular antiviral responses. Among the best characterized is the shutoff of protein synthesis mediated by the dsRNA-dependent protein kinase (PKR) and the oligoadenylate synthetase (OAS)/RNase L system. As viral replication depends on protein synthesis, many viruses have evolved mechanisms for counteracting the PKR and OAS/RNase L pathways. The murine cytomegalovirus (MCMV) proteins m142 and m143 have been characterized as dsRNA binding proteins that inhibit PKR activation, phosphorylation of the translation initiation factor eIF2α, and a subsequent protein synthesis shutoff. In the present study we analyzed the contribution of the PKR- and the OAS-dependent pathways to the control of MCMV replication in the absence or presence of m142 and m143. We show that the induction of eIF2α phosphorylation during infection with an m142- and m143-deficient MCMV is specifically mediated by PKR, not by the related eIF2α kinases PERK or GCN2. PKR antagonists of vaccinia virus (E3L) or herpes simplex virus (γ34.5) rescued the replication defect of an MCMV strain with deletions of both m142 and m143. Moreover, m142 and m143 bound to each other and interacted with PKR. By contrast, an activation of the OAS/RNase L pathway by MCMV was not detected in the presence or absence of m142 and m143, suggesting that these viral proteins have little or no influence on this pathway. Consistently, an m142- and m143-deficient MCMV strain replicated to high titers in fibroblasts lacking PKR but did not replicate in cells lacking RNase L. Hence, the PKR-mediated antiviral response is responsible for the essentiality of m142 and m143.
Infectious Molecular Clones of Adeno-Associated Virus Isolated Directly from Human Tissues
Authors: Schnepp Bruce C. , Jensen Ryan L. , Clark K. Reed , Johnson Philip R. 
Published: November 2008

ABSTRACT
Adeno-associated virus (AAV) replication and biology have been extensively studied using cell culture systems, but there is precious little known about AAV biology in natural hosts. As part of our ongoing interest in the in vivo biology of AAV, we previously described the existence of extrachromosomal proviral AAV genomes in human tissues. In the current work, we describe the molecular structure of infectious DNA clones derived directly from these tissues. Sequence-specific linear rolling-circle amplification was utilized to isolate clones of native circular AAV DNA. Several molecular clones containing unit-length viral genomes directed the production of infectious wild-type AAV upon DNA transfection in the presence of adenovirus help. DNA sequence analysis of the molecular clones revealed the ubiquitous presence of a double-D inverted terminal repeat (ITR) structure, which implied a mechanism by which the virus is able to maintain ITR sequence continuity and persist in the absence of host chromosome integration. These data suggest that the natural life cycle of AAV, unlike that of retroviruses, might not have genome integration as an obligatory component.
Signaling through Toll-Like Receptors Induces Murine Gammaherpesvirus 68 Reactivation In Vivo
Authors: Gargano Lisa M. , Forrest J. Craig , Speck Samuel H. 
Published: November 2008

ABSTRACT

Murine gammaherpesvirus 68 (MHV68) establishes a lifelong infection in mice and is used as a model pathogen to study the role of viral and host factors in chronic infection. The maintenance of chronic MHV68 infection, at least in some latency reservoirs, appears to be dependent on the capacity of the virus to reactivate from latency in vivo. However, the signals that lead to MHV68 reactivation in vivo are not well characterized. Toll-like receptors (TLRs), by recognizing the specific patterns of microbial components, play an essential role in the activation of innate immunity. In the present study, we investigated the capacity of TLR ligands to induce MHV68 reactivation, both in vitro and in vivo. The stimulation of latently infected B cell lines with ligands for TLRs 3, 4, 5, and 9 enhanced MHV68 reactivation; the ex vivo stimulation of latently infected primary splenocytes, recovered from infected mice, with poly(I:C), lipopolysaccharide, flagellin, or CpG DNA led to early B-cell activation, B-cell proliferation, and a significant increase in the frequency of latently infected cells reactivating the virus. In vivo TLR stimulation also induced B-cell activation and MHV68 reactivation, resulting in heightened levels of virus replication in the lungs which correlated with an increase in MHV68-specific CD8
+
T-cell responses. Importantly, TLR stimulation also led to an increase in MHV68 latency, as evidenced by an increase in viral genome-positive cells 2 weeks post-in vivo stimulation by specific TLR ligands. Thus, these data demonstrate that TLR stimulation can drive MHV68 reactivation from latency and suggests that periodic pathogen exposure may contribute to the homeostatic maintenance of chronic gammaherpesvirus infection through stimulating virus reactivation and reseeding latency reservoirs.