bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clonal Evolution Leading to Maintenance of Antibiotic Resistance Rates among Colonizing Pneumococci in the PCV7 Era in Portugal
Authors: Simões Alexandra S. , Pereira Liliana , Nunes Sónia , Brito-Avô António , de Lencastre Hermínia , Sá-Leão Raquel 
Published: June 2011

ABSTRACT

The introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in Portugal led to extensive serotype replacement among carriers of pneumococci, with a marked decrease of PCV7 types. Although antimicrobial resistance was traditionally associated with PCV7 types, no significant changes in the rates of nonsusceptibility to penicillin, resistance to macrolides, or multidrug resistance were observed. This study aimed to investigate the mechanisms leading to maintenance of antimicrobial resistance, despite marked serotype replacement. We compared, through molecular typing, 252 antibiotic-resistant pneumococci recovered from young carriers in 2006 and 2007 (era of high PCV7 uptake) with collections of isolates from 2002 and 2003 (
n
=374; low-PCV7-uptake era) and 1996 to 2001 (
n
=805; pre-PCV7 era). We observed that the group of clones that has accounted for antimicrobial resistance since 1996 is essentially the same as the one identified in the PCV7 era. The relative proportions of such clones have, however, evolved substantially overtime. Notably, widespread use of PCV7 led to an expansion of two Pneumococcal Molecular Epidemiology Network (PMEN) clones expressing non-PCV7 capsular variants of the original strains: Sweden
15A
ST63 (serotypes 15A and 19A) and Denmark
14
ST230 (serotypes 19A and 24F). These variants were already in circulation in the pre-PCV7 era, although they have now become increasingly abundant. Emergence of novel clones and
de novo
acquisition of resistance contributed little to the observed scenario. No evidence of capsular switch events occurring after PCV7 introduction was found. In the era of PCVs, antimicrobial resistance remains a problem among the carried pneumococci. Continuous surveillance is warranted to evaluate serotype and clonal shifts leading to maintenance of antimicrobial resistance.
Poly(C)-Binding Protein 2 Interacts with Sequences Required for Viral Replication in the Hepatitis C Virus (HCV) 5′ Untranslated Region and Directs HCV RNA Replication through Circularizing the Viral Genome
Authors: Wang Linya , Jeng King-Song , Lai Michael M. C. 
Published: June 2011

ABSTRACT

Sequences in the 5′ untranslated region (5′UTR) of hepatitis C virus (HCV) RNA is important for modulating both translation and RNA replication. The translation of the HCV genome depends on an internal ribosome entry site (IRES) located within the 341-nucleotide 5′UTR, while RNA replication requires a smaller region. A question arises whether the replication and translation functions require different regions of the 5′UTR and different sets of RNA-binding proteins. Here, we showed that the 5′-most 157 nucleotides of HCV RNA is the minimum 5′UTR for RNA replication, and it partially overlaps with the IRES. Stem-loops 1 and 2 of the 5′UTR are essential for RNA replication, whereas stem-loop 1 is not required for translation. We also found that poly(C)-binding protein 2 (PCBP2) bound to the replication region of the 5′UTR and associated with detergent-resistant membrane fractions, which are the sites of the HCV replication complex. The knockdown of PCBP2 by short hairpin RNA decreased the amounts of HCV RNA and nonstructural proteins. Antibody-mediated blocking of PCBP2 reduced HCV RNA replication
in vitro
, indicating that PCBP2 is directly involved in HCV RNA replication. Furthermore, PCBP2 knockdown reduced IRES-dependent translation preferentially from a dual reporter plasmid, suggesting that PCBP2 also regulated IRES activity. These findings indicate that PCBP2 participates in both HCV RNA replication and translation. Moreover, PCBP2 interacts with HCV 5′- and 3′UTR RNA fragments to form an RNA-protein complex and induces the circularization of HCV RNA, as revealed by electron microscopy. This study thus demonstrates the mechanism of the participation of PCBP2 in HCV translation and replication and provides physical evidence for HCV RNA circularization through 5′- and 3′UTR interaction.
Genomic and Proteomic Analysis of Invertebrate Iridovirus Type 9
Authors: Wong Chun K. , Young Vivienne L. , Kleffmann Torsten , Ward Vernon K. 
Published: June 2011

ABSTRACT

Iridoviruses (IV) are nuclear cytoplasmic large DNA viruses that are receiving increasing attention as sublethal pathogens of a range of insects. Invertebrate iridovirus type 9 (IIV-9; Wiseana iridovirus) is a member of the major phylogenetic group of iridoviruses for which there is very limited genomic and proteomic information. The genome is 205,791 bp, has a G+C content of 31%, and contains 191 predicted genes, with approximately 20% of its repeat sequences being located predominantly within coding regions. The repeated sequences include 11 proteins with helix-turn-helix motifs and genes encoding related tandem repeat amino acid sequences. Of the 191 proteins encoded by IIV-9, 108 are most closely related to orthologs in IIV-3 (
Chloriridovirus
genus), and 114 of the 126 IIV-3 genes have orthologs in IIV-9. In contrast, only 97 of 211 IIV-6 genes have orthologs in IIV-9. There is almost no conservation of gene order between IIV-3, IIV-6, and IIV-9. Phylogenetic analysis using a concatenated sequence of 26 core IV genes confirms that IIV-3 is more closely related to IIV-9 than to IIV-6, despite being from a different genus of the
Iridoviridae
. An interaction between IIV and small RNA regulatory systems is supported by the prediction of seven putative microRNA (miRNA) sequences combined with XRN exonuclease, RNase III, and double-stranded RNA binding activities encoded on the genome. Proteomic analysis of IIV-9 identified 64 proteins in the virus particle and, when combined with infected cell analysis, confirmed the expression of 94 viral proteins. This study provides the first full-genome and consequent proteomic analysis of group II IIV.
The 2.3-Angstrom Structure of Porcine Circovirus 2
Authors: Khayat Reza , Brunn Nicholas , Speir Jeffrey A. , Hardham John M. , Ankenbauer Robert G. , Schneemann Anette , Johnson John E. 
Published: June 2011

ABSTRACT
Porcine circovirus 2 (PCV2) is a T=1 nonenveloped icosahedral virus that has had severe impact on the swine industry. Here we report the crystal structure of an N-terminally truncated PCV2 virus-like particle at 2.3-Å resolution, and the cryo-electron microscopy (cryo-EM) image reconstruction of a full-length PCV2 virus-like particle at 9.6-Å resolution. This is the first atomic structure of a circovirus. The crystal structure revealed that the capsid protein fold is a canonical viral jelly roll. The loops connecting the strands of the jelly roll define the limited features of the surface. Sulfate ions interacting with the surface and electrostatic potential calculations strongly suggest a heparan sulfate binding site that allows PCV2 to gain entry into the cell. The crystal structure also allowed previously determined epitopes of the capsid to be visualized. The cryo-EM image reconstruction showed that the location of the N terminus, absent in the crystal structure, is inside the capsid. As the N terminus was previously shown to be antigenic, it may externalize through viral “breathing.”
Human Dendritic Cells Infected with the Nonpathogenic Mopeia Virus Induce Stronger T-Cell Responses than Those Infected with Lassa Virus
Authors: Pannetier Delphine , Reynard Stéphanie , Russier Marion , Journeaux Alexandra , Tordo Noël , Deubel Vincent , Baize Sylvain 
Published: June 2011

ABSTRACTThe events leading to death in severe cases of Lassa fever (LF) are unknown. Fatality seems to be linked to high viremia and immunosuppression, and cellular immunity, rather than neutralizing antibodies, appears to be essential for survival. We previously compared Lassa virus (LV) with its genetically close but nonpathogenic homolog Mopeia virus (MV), which was used to model nonfatal LF. We showed that strong and early activation of antigen-presenting cells (APC) may play a crucial role in controlling infection. Here we developed anin vitromodel of dendritic-cell (DC)-T-cell coculture in order to characterize human T-cell responses induced by MV- or LV-infected DCs. Our results show very different responses to infection with LV and MV. MV strongly and durably stimulated CD8+and CD4+T cells, showing early and high activation, a strong proliferative response, and acquisition of effector and memory phenotypes. Furthermore, robust and functional CD4+and CD8+cytotoxic T lymphocytes (CTL) were generated. LV, however, induced only weak memory responses. Thus, this study allows an improved understanding of the pathogenesis and immune mechanisms involved in the control of human LV.
Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells
Authors: Connolly-Andersen Anne-Marie , Moll Guido , Andersson Cecilia , Åkerström Sara , Karlberg Helen , Douagi Iyadh , Mirazimi Ali 
Published: June 2011

ABSTRACT
Crimean-Congo hemorrhagic fever virus (CCHFV) causes viral hemorrhagic fever with high case-fatality rates and is geographically widely distributed. Due to the requirement for a biosafety level 4 (BSL-4) laboratory and the lack of an animal model, knowledge of the viral pathogenesis is limited. Crimean-Congo hemorrhagic fever (CCHF) is characterized by hemorrhage and vascular permeability, indicating the involvement of endothelial cells (ECs). The interplay between ECs and CCHFV is therefore important for understanding the pathogenesis of CCHF. In a previous study, we found that CCHFV-infected monocyte-derived dendritic cells (moDCs) activated ECs; however, the direct effect of CCHFV on ECs was not investigated. Here, we report that ECs are activated upon infection, as demonstrated by upregulation of mRNA levels for E-selectin, vascular cell adhesion molecule 1 (VCAM1), and intercellular adhesion molecule 1 (ICAM1). Protein levels and cell surface expression of ICAM1 responded in a dose-dependent manner to increasing CCHFV titers with concomitant increase in leukocyte adhesion. Furthermore, we examined vascular endothelial (VE) cadherin in CCHFV-infected ECs by different approaches. Infected ECs released higher levels of interleukin 6 (IL-6) and IL-8; however, stimulation of resting ECs with supernatants derived from infected ECs did not result in increased ICAM1 expression. Interestingly, the moDC-mediated activation of ECs was abrogated by addition of neutralizing tumor necrosis factor alpha (TNF-α) antibody to moDC supernatants, thereby identifying this soluble mediator as the key cytokine causing EC activation. We conclude that CCHFV can exert both direct and indirect effects on ECs.
Detection of Minority Resistance during Early HIV-1 Infection: Natural Variation and Spurious Detection rather than Transmission and Evolution of Multiple Viral Variants
Authors: Gianella Sara , Delport Wayne , Pacold Mary E. , Young Jason A. , Choi Jun Yong , Little Susan J. , Richman Douglas D. , Kosakovsky Pond Sergei L. , Smith Davey M. 
Published: June 2011

ABSTRACT

Reports of a high frequency of the transmission of minority viral populations with drug-resistant mutations (DRM) are inconsistent with evidence that HIV-1 infections usually arise from mono- or oligoclonal transmission. We performed ultradeep sequencing (UDS) of partial HIV-1
gag
,
pol
, and
env
genes from 32 recently infected individuals. We then evaluated overall and per-site diversity levels, selective pressure, sequence reproducibility, and presence of DRM and accessory mutations (AM). To differentiate biologically meaningful mutations from those caused by methodological errors, we obtained multinomial confidence intervals (CI) for the proportion of DRM at each site and fitted a binomial mixture model to determine background error rates for each sample. We then examined the association between detected minority DRM and the virologic failure of first-line antiretroviral therapy (ART). Similar to other studies, we observed increased detection of DRM at low frequencies (average, 0.56%; 95% CI, 0.43 to 0.69; expected UDS error, 0.21 ± 0.08% mutations/site). For 8 duplicate runs, there was variability in the proportions of minority DRM. There was no indication of increased diversity or selection at DRM sites compared to other sites and no association between minority DRM and AM. There was no correlation between detected minority DRM and clinical failure of first-line ART. It is unlikely that minority viral variants harboring DRM are transmitted and maintained in the recipient host. The majority of low-frequency DRM detected using UDS are likely errors inherent to UDS methodology or a consequence of error-prone HIV-1 replication.
Can we accredit hospital ethics? A tentative proposal
Authors: Wu Min-Hua , Liao Chih-Hsien , Chiu Wen-Ta , Lin Ching-Ying , Yang Che-Ming 
Published: June 2011

ObjectivesThe objective of this research was to develop ethics accreditation standards for hospitals.Research designOur research methods included a literature review, an expert focus group, the Delphi technique and a hospital survey. The entire process was separated into two stages: (1) the development of a draft of hospital ethics accreditation standards; and (2) conducting a nationwide hospital survey of the proposed standards.ResultsThis study produced a tentative draft of hospital ethics accreditation standards comprised of six chapters and 62 standards based on the expert focus group and Delphi technique. The six chapters are: Medical ethics policies, regulations and leadership; The establishment and operation of a medical ethics committee; The establishment and operation of research-related ethics committees; Medical ethics education; Organisational ethical climate; and Respect for patients' rights and establishment of good hospital-patient relationships. The hospital survey indicated that the concept of an organisational ethical climate was new to most hospital managers, most hospitals disliked the idea of having a separate hospital ethics accreditation system, and small hospitals were concerned about their ability to comply with all of the standards.ConclusionsRegardless of whether hospital ethics accreditation can be a stand-alone accreditation or just part of existing hospital accreditation programmes, we hope this draft can serve as a good reference for future endeavours by hospital accreditation authorities.
Waterpipe tobacco products: nicotine labelling versus nicotine delivery
Authors: Vansickel Andrea R , Shihadeh Alan , Eissenberg Thomas 
Published: June 2011

BackgroundWaterpipe tobacco package labelling typically indicates “0.0% tar” and “0.05% or 0.5% nicotine”.ObjectiveTo determine the extent to which nicotine labeling is related to nicotine delivery.Methods110 waterpipe smokers engaged in a 45-minute waterpipe smoking session. Puff topography and plasma nicotine were measured. Three waterpipe tobacco brands were used: Nakhla (0.5% nicotine), Starbuzz (0.05% nicotine), and Al Fakher (0.05% nicotine). Data were analyzed by one-way ANOVA.ResultsTopography did not differ across brands. Peak plasma nicotine varied significantly across brands. Al Fakher had the highest nicotine delivery (11.4 ng/ml) followed by Nakhla (9.8 ng/ml) and Starbuzz (5.8 ng/ml).ConclusionsNicotine labelling on waterpipe tobacco products does not reflect delivery; smoking a brand with a “0.05% nicotine” label led to greater plasma nicotine levels than smoking a brand with a “0.5% nicotine” label. Waterpipe tobacco products should be labelled in a manner that does not mislead consumers.
In planta reduction of maize seedling stalk lesions by the bacterial endophyteBacillus mojavensis
Authors: Bacon Charles W. , Hinton Dorothy M. 
Published: June 2011

Maize ( Zea mays L.) is susceptible to infection by Fusarium verticillioides through autoinfection and alloinfection, resulting in diseases and contamination of maize kernels with the fumonisin mycotoxins. Attempts at controlling this fungus are currently being done with biocontrol agents such as bacteria, and this includes bacterial endophytes, such as Bacillus mojavensis . In addition to producing fumonisins, which are phytotoxic and mycotoxic, F. verticillioides also produces fusaric acid, which acts both as a phytotoxin and as an antibiotic. The question now is Can B. mojavensis reduce lesion development in maize during the alloinfection process, simulated by internode injection of the fungus? Mutant strains of B. mojavensis that tolerate fusaric acid were used in a growth room study to determine the development of stalk lesions, indicative of maize seedling blight, by co-inoculations with a wild-type strain of F. verticillioides and with non-fusaric acid producing mutants of F. verticillioides. Lesions were measured on 14-day-old maize stalks consisting of treatment groups inoculated with and without mutants and wild-type strains of bacteria and fungi. The results indicate that the fusaric-acid-tolerant B. mojavensis mutant reduced stalk lesions, suggesting an in planta role for this substance as an antibiotic. Further, lesion development occurred in maize infected with F. verticillioides mutants that do not produce fusaric acid, indicating a role for other phytotoxins, such as the fumonisins. Thus, additional pathological components should be examined before strains of B. mojavensis can be identified as being effective as a biocontrol agent, particularly for the control of seedling disease of maize.
Mechanism of acid tolerance in a rhizobium strain isolated from Pueraria lobata (Willd.) Ohwi
Authors: Lei Zhang , Jian-ping Gu , Shi-qing Wei , Ze-yang Zhou , Chao Zhang , Yongxiong Yu 
Published: June 2011

The Rhizobium sp. strain PR389 was isolated from the root nodules of Pueraria lobata (Willd.) Ohwi, which grows in acidic (pH 4.6) yellow soil of the Jinyun Mountains of Beibei, Chongqing, China. While rhizobia generally have a pH range of 6.5–7.5 for optimum growth, strain PR389 grew in a liquid yeast extract – mannitol agar medium at pH 4.6, as well as in a pH 4.1 soil suspension, suggesting acid tolerance in this specific strain of rhizobium . However, at pH 4.6, the lag phase before vigorous growth was 40 h compared with 4 h under neutral conditions (pH 7.0). For PR389, the generation time after the lag phase remained the same at different pH levels despite the different durations of the lag phase. Except in the pH 4.4 treatment, the pH of the culturing media increased from 4.6, 4.8, 5.0, and 5.5 to neutral and slightly alkaline after 70 h of culture. Chloramphenicol was added to determine if protein production was involved in the increasing pH process. Chloramphenicol significantly inhibited PR389 growth under acid stress but had little effect under neutral conditions. Proton flux measured during a short acid shock (pH 3.8) revealed that this strain has an intrinsic ability to prevent H+ from entering cells when compared with acid-sensitive rhizobia. We propose that the mechanism for acid tolerance in PR389 involves both intracellular and extracellular processes. When the extracellular pH is lower than pH 4.4, the cell membrane blocks hydrogen from entering the cell. When the pH exceeds 4.4, the rhizobium strain has the ability to raise the extracellular pH, thereby, potentially decreasing the toxicity of aluminum in acid soil.
Telmisartan provides protection against development of impaired vasodilation independently of metabolic effects in SHRSP.Z-Leprfa/IzmDmcr rats with metabolic syndrome
Authors: Kagota Satomi , Tada Yukari , Nejime Namie , Nakamura Kazuki , Kunitomo Masaru , Shinozuka Kazumasa 
Published: June 2011

Metabolic syndrome is known to facilitate the development of cardiovascular disease. We have demonstrated that mesenteric arteries of SHRSP.Z-Leprfa/IzmDmcr (SHRSP-fatty) rats with metabolic syndrome display an impaired vasorelaxation response mediated by nitric oxide. We examined whether the condition could be alleviated by treatment with telmisartan, an angiotensin II type 1 (AT1) receptor antagonist with PPAR-γ-activating properties and compared the results with those from pioglitazone, a PPAR-γ agonist. Telmisartan (5 mg·kg–1·day–1) or pioglitazone (2.5 mg·kg–1·day–1) was orally administered to male SHRSP-fatty rats for 8 weeks. Serum triglyceride and cholesterol levels were determined, and the oral glucose tolerance test was performed to evaluate insulin resistance. Vasodilations in response to acetylcholine and nitroprusside were determined by wire myographs under isometric tension conditions, protein expressions of soluble guanylyl cyclase in mesenteric arteries by Western blotting, and the contents of 3-nitrotyrosine in aortas by high-performance liquid chromatography with electrochemical detection. Telmisartan exerted antihypertensive effects, while pioglitazone ameliorated metabolic abnormalities in SHRSP-fatty rats. Telmisartan increased acetylcholine- and nitroprusside-induced relaxation and soluble guanylyl cyclase protein expression in mesenteric arteries and reduced 3-nitrotyrosine content in aortas. Pioglitazone displayed no such alleviating effects on vascular functions. These findings indicate that telmisartan protects against vasodilation disturbance through anti-oxidative and -nitrative stress independently of metabolic effects in SHRSP-fatty rats with metabolic syndrome.
When animals are not quite what they eat: diet digestibility influences13C-incorporation rates and apparent discrimination in a mixed-feeding herbivore
Authors: Codron Daryl , Codron Jacqui , Sponheimer Matt , Bernasconi Stefano M. , Clauss Marcus 
Published: June 2011

The stable carbon isotope composition of animal tissues represents the weighted sum of the variety of food sources eaten. If sources differ in digestibility, tissues may overrepresent intake of more digestible items and faeces may overrepresent less digestible items. We tested this idea using whole blood and faeces of goats ( Capra hircus L., 1758) fed different food mixtures of C3lucerne ( Medicago sativa L.) and C4grass ( Themeda triandra Forssk.). Although blood and faecal δ13C values were broadly consistent with diet, results indicate mismatch between consumer and diet isotope compositions: both materials overrepresented the C3(lucerne) component of diets. Lucerne had lower fibre digestibility than T. triandra, which explains the results for faeces, whereas underrepresentation of dietary C4in blood is consistent with low protein content of the grass hay. A diet switch experiment revealed an important difference in13C-incorporation rates across diets, which were slower for grass than lucerne diets, and in fact equilibrium states were not reached for all diets. Although more research is needed to link digestive kinetics with isotope incorporation, these results provide evidence for nonlinear relationships between consumers and their diets, invoking concerns about the conceptual value of “discrimination factors” as the prime currency for contemporary isotope ecology.