bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid Identification of Methicillin-Resistant
Staphylococcus aureus
Transmission in Hospitals by Use of Phage-Derived Open Reading Frame Typing Enhanced by Multiplex PCR and Reverse Line Blot Assay
Authors: O'Sullivan Matthew V. N. , Kong Fanrong , Sintchenko Vitali , Gilbert Gwendolyn L. 
Published: June 2010

ABSTRACT

The relatively high-level clonality of methicillin-resistant
Staphylococcus aureus
(MRSA) and its frequent high-level endemicity in nosocomial settings complicate the development of methods for rapid subtyping of MRSA strains that are capable of identifying person-to-person transmission in hospitals. Phage-derived open reading frame (PDORF) typing is an MRSA typing method targeting mobile genetic elements that was recently described and evaluated using a geographically restricted set of isolates. The objective of this study was to develop a multiplex PCR-reverse line blot (mPCR/RLB) assay for PDORF typing and to test its applicability on a broad range of isolates and in an environment where MRSA is highly endemic. The 16 targets were identified using a 23-primer-pair mPCR/RLB assay with two probes for each target. The method was evaluated using 42 MRSA reference strains, including those representing major international clones, and 35 isolates from episodes of suspected nosocomial transmission.
In vivo
stability was explored using 81 isolate pairs. Pulsed-field gel electrophoresis (PFGE) and
spa
typing were performed for comparison. Among the 42 reference strains, there were 33 PFGE subtypes, 30 PDORF types, and 22
spa
types. Simpson's index of diversity was 0.987, 0.971, and 0.926 for PFGE subtyping, PDORF typing, and
spa
typing, respectively. Typing of clinical isolates by PDORF typing and PFGE demonstrated concordant results. mPCR/RLB-based PDORF typing has similar discriminatory power to that of PFGE, can assist in tracking MRSA transmission events in a setting of high-level endemicity, and has the advantage of being a high-throughput technique.
Subcutaneous
Mycoleptodiscus indicus
Infection in an Immunosuppressed Dog
Authors: Metry Catherine A. , Hoien-Dalen Patricia S. , Maddox Carol W. , Thompson Elizabeth H. , Sutton Deanna A. , Romanelli Anna M. , Wickes Brian L. , MacNeill Amy L. 
Published: June 2010

ABSTRACT

An 8-year-old dog presented with several dermal excoriations. Lesion cytology revealed pyogranulomatous inflammation with branching, septate hyphae. A mold identified as
Mycoleptodiscus indicus
by morphology and sequencing was cultured from fine-needle aspirates. This is the first report of a
Mycoleptodiscus
species as an etiologic agent in a dog.
Recovery of Replication-Competent Residual HIV-1 from Plasma of a Patient Receiving Prolonged, Suppressive Highly Active Antiretroviral Therapy
Authors: Sahu Gautam K. , Sarria Juan C. , Cloyd Miles W. 
Published: June 2010

ABSTRACT

The clinical significance of persistent residual viremia in patients on prolonged highly active antiretroviral therapy (HAART) is not clear. Moreover, it remains to be demonstrated whether residual viremia consists of viruses capable of spreading infection
in vivo
upon termination of therapy. Using residual viral RNAs (vRNAs) isolated from a HAART-treated patient's plasma, we cloned full-length viral genomes and found that most of them could produce infectious, replication-competent HIVs when transfected into TZM-bl cells, suggesting that residual viruses produced in the absence of therapy can initiate fresh cycles of infection and spread in host cells. The data further indicate that residual viremia may pose a major concern with regard to the emergence of drug-resistant HIVs during periods of low adherence to therapy.
Role of Noncovalent SUMO Binding by the Human Cytomegalovirus IE2 Transactivator in Lytic Growth
Authors: Kim Eui Tae , Kim Young-Eui , Huh Yong Ho , Ahn Jin-Hyun 
Published: June 2010

ABSTRACT
The 86-kDa immediate-early 2 (IE2) protein of human cytomegalovirus (HCMV) is a promiscuous transactivator essential for viral gene expression. IE2 is covalently modified by SUMO at two lysine residues (K175 and K180) and also interacts noncovalently with SUMO. Although SUMOylation of IE2 has been shown to enhance its transactivation activity, the role of SUMO binding is not clear. Here we showed that SUMO binding by IE2 is necessary for its efficient transactivation function and for viral growth. IE2 bound physically to SUMO-1 through a SUMO-interacting motif (SIM). Mutations in SIM (mSIM) or in both SUMOylation sites and SIM (KR/mSIM), significantly reduced IE2 transactivation effects on viral early promoters. The replication of IE2 SIM mutant viruses (mSIM or KR/mSIM) was severely depressed in normal human fibroblasts. Analysis of viral growth curves revealed that the replication defect of the mSIM virus correlated with low-level accumulation of SUMO-modified IE2 and of viral early and late proteins. Importantly, both the formation of viral transcription domains and the association of IE2 with viral promoters in infected cells were significantly reduced in IE2 SIM mutant virus infection. Furthermore, IE2 was found to interact with the SUMO-modified form of TATA-binding protein (TBP)-associated factor 12 (TAF12), a component of the TFIID complex, in a SIM-dependent manner, and this interaction enhanced the transactivation activity of IE2. Our data demonstrate that the interaction of IE2 with SUMO-modified proteins plays an important role for the progression of the HCMV lytic cycle, and they suggest a novel viral mechanism utilizing the cellular SUMO system.
Limited Contribution of Mucosal IgA to Simian Immunodeficiency Virus (SIV)-Specific Neutralizing Antibody Response and Virus Envelope Evolution in Breast Milk of SIV-Infected, Lactating Rhesus Monkeys
Authors: Permar Sallie R. , Wilks Andrew B. , Ehlinger Elizabeth P. , Kang Helen H. , Mahlokozera Tatenda , Coffey Rory T. , Carville Angela , Letvin Norman L. , Seaman Michael S. 
Published: June 2010

ABSTRACTBreast milk transmission of human immunodeficiency virus (HIV) remains an important mode of infant HIV acquisition. Interestingly, the majority of infants remain uninfected during prolonged virus exposure via breastfeeding, raising the possibility that immune components in milk prevent mucosal virus transmission. HIV-specific antibody responses are detectable in the milk of HIV-infected women and simian immunodeficiency virus (SIV)-infected monkeys; however, the role of these humoral responses in virus neutralization and local virus quasispecies evolution has not been characterized. In this study, four lactating rhesus monkeys were inoculated with SIVmac251 and monitored for SIV envelope-specific humoral responses and virus evolution in milk and plasma throughout infection. While the kinetics and breadth of the SIV-specific IgG and IgA responses in milk were similar to those in plasma, the magnitude of the milk responses was considerably lower than that of the plasma responses. Furthermore, a neutralizing antibody response against the inoculation virus was not detected in milk samples at 1 year after infection, despite a measurable autologous neutralizing antibody response in plasma samples obtained from three of four monkeys. Interestingly, while IgA is the predominant immunoglobulin in milk, the milk SIV envelope-specific IgA response was lower in magnitude and demonstrated more limited neutralizing capacity against a T-cell line-adapted SIV compared to those of the milk IgG response. Finally, amino acid mutations in the envelope gene product of SIV variants in milk and plasma samples occurred in similar numbers and at similar positions, indicating that the humoral immune pressure in milk does not drive distinct virus evolution in the breast milk compartment.
A Nine-Segment Influenza A Virus Carrying Subtype H1 and H3 Hemagglutinins
Authors: Gao Qinshan , Lowen Anice C. , Wang Taia T. , Palese Peter 
Published: June 2010

ABSTRACTInfluenza virus genomic RNAs possess segment-specific packaging signals that include both noncoding regions (NCRs) and adjacent terminal coding region sequences. Using reverse genetics, an A/Puerto Rico/8/34 (A/PR/8/34) virus was rescued that contained a modified PB1 gene such that the PB1 packaging sequences were exchanged for those of the neuraminidase (NA) gene segment. To accomplish this, the PB1 open reading frame, in which the terminal packaging signals were inactivated by serial synonymous mutations, was flanked by the NA segment-specific packaging sequences including the NCRs and the coding region packaging signals. Next, the ATGs located on the 3′ end of the NA packaging sequences of the resulting PB1 chimeric segment were mutated to allow for correct translation of the full-length PB1 protein. The virus containing this chimeric PB1 segment was viable and able to stably carry a ninth, green fluorescent protein (GFP), segment flanked by PB1 packaging signals. Utilizing this method, we successfully generated an influenza virus that contained the genes coding for both the H1 hemagglutinin (HA) from A/PR/8/34 and the H3 HA from A/Hong Kong/1/68 (A/HK/1/68); both subtypes of HA protein were also incorporated into the viral envelope. Immunization of mice with this recombinant virus conferred complete protection from lethal challenge with recombinant A/PR/8/34 virus and with X31 virus that expresses the A/HK/1/68 HA and NA. Using the described methodology, we show that a ninth segment can also be incorporated by manipulation of the PB2 or PA segment-specific packaging signals. This approach offers a means of generating a bivalent influenza virus vaccine.
The Localization of APOBEC3H Variants in HIV-1 Virions Determines Their Antiviral Activity
Authors: Ooms Marcel , Majdak Susan , Seibert Christopher W. , Harari Ariana , Simon Viviana 
Published: June 2010

ABSTRACT

Several members of the human APOBEC3 family of cytidine deaminases can potently restrict retroviruses such as HIV-1. The single-domain APOBEC3H (A3H) is encoded by four haplotypes, of which only A3H haplotype II-RDD (hapII-RDD) restricts HIV-1 efficiently. The goal of this study was to elucidate the mechanisms underlying the differences in antiviral activity among A3H haplotypes. The naturally occurring A3H hapI-GKE and hapII-RDD variants differ at three amino acid positions. A panel of six site-directed mutants containing combinations of the three variable residues was used to determine A3H protein expression, requirements of A3H virion incorporation, and A3H-Gag interactions. The catalytic activity of each A3H protein was assessed directly by using an
Escherichia coli
mutator assay. We found that the incorporation efficiencies of A3H variants into HIV-1 virions were comparable despite major differences in cellular expression. An assessment of the enzymes' catalytic activities showed that the deaminase activity of each A3H variant correlated with protein expression, suggesting similar enzymatic efficiencies. Surprisingly, virion incorporation experiments using Gag deletion mutants demonstrated that A3H haplotypes interacted with different Gag regions. A3H hapII-RDD associated with nucleocapsid in an RNA-dependent manner, whereas A3H hapI-GKE associated with the C-terminal part of matrix and the N-terminal capsid domain. Our results show that the A3H hapII-RDD interaction with nucleocapsid is critical for its antiviral activity and that the inability of A3H hapI-GKE to interact with nucleocapsid underlies its limited antiviral potential. Thus, the antiviral activity of A3H haplotypes is determined by its incorporation into the viral core, in proximity to the reverse transcription complex.
A Stretch of 11 Amino Acids in the βB-βC Loop of the Coat Protein of
Grapevine Fanleaf Virus
Is Essential for Transmission by the Nematode
Xiphinema index
Authors: Schellenberger Pascale , Andret-Link Peggy , Schmitt-Keichinger Corinne , Bergdoll Marc , Marmonier Aurélie , Vigne Emmanuelle , Lemaire Olivier , Fuchs Marc , Demangeat Gérard , Ritzenthaler Christophe 
Published: June 2010

ABSTRACT

Grapevine fanleaf virus
(GFLV) and
Arabis mosaic virus
(ArMV) from the genus
Nepovirus
, family
Secoviridae
, cause a severe degeneration of grapevines. GFLV and ArMV have a bipartite RNA genome and are transmitted specifically by the ectoparasitic nematodes
Xiphinema index
and
Xiphinema diversicaudatum
, respectively. The transmission specificity of both viruses maps to their respective RNA2-encoded coat protein (CP). To further delineate the GFLV CP determinants of transmission specificity, three-dimensional (3D) homology structure models of virions and CP subunits were constructed based on the crystal structure of
Tobacco ringspot virus
, the type member of the genus
Nepovirus
. The 3D models were examined to predict amino acids that are exposed at the external virion surface, highly conserved among GFLV isolates but divergent between GFLV and ArMV. Five short amino acid stretches that matched these topographical and sequence conservation criteria were selected and substituted in single and multiple combinations by their ArMV counterparts in a GFLV RNA2 cDNA clone. Among the 21 chimeric RNA2 molecules engineered, transcripts of only three of them induced systemic plant infection in the presence of GFLV RNA1. Nematode transmission assays of the three viable recombinant viruses showed that swapping a stretch of (i) 11 residues in the βB-βC loop near the icosahedral 3-fold axis abolished transmission by
X. index
but was insufficient to restore transmission by
X. diversicaudatum
and (ii) 7 residues in the βE-αB loop did not interfere with transmission by the two
Xiphinema
species. This study provides new insights into GFLV CP determinants of nematode transmission.
Possible effect of environmental exposure to asbestos on geographical variation in mesothelioma rates
Authors: Goldberg Stephen , Rey Grégoire , Luce Danièle , Gilg Soit Ilg Anabelle , Rolland Patrick , Brochard Patrick , Imbernon Ellen , Goldberg Marcel 
Published: June 2010

BackgroundIn population-based mesothelioma studies in industrialised countries, the incidence of mesothelioma without any identified asbestos exposure (IAE) is usually higher among women, while male incidence is mainly attributed to IAE. Through a comparison of the spatial distribution of male and female rates, and IAE and no IAE incidence, this study investigated whether mesotheliomas without IAE are in fact induced by non-recognised asbestos exposure, mostly from environmental sources.MethodsWe calculated mesothelioma mortality (SMR) and incidence (SIR) ratios by district in France, pooling 30 and 10 years of data, respectively. Using correlation coefficients, we compared geographical patterns of male and female mesothelioma ratios, and IAE and no IAE mesothelioma ratios.ResultsThe raw numbers of male and female mesothelioma cases were equivalent. Mesothelioma SMR (0.76) and SIR (0.80) geographical correlations between men and women were strongly positive. SIR correlation between occupationally IAE and no IAE cases was also positive (0.69). Correlation between occupationally IAE and no IAE cases was positive among women but not among men.ConclusionsData analyses of mesothelioma mortality and incidence showed that female cases occur in the same geographical areas as male cases. Female mesotheliomas with no IAE occur in the same geographical areas as exposed cases, suggesting asbestos has a major influence on female mesothelioma, likely through environmental exposure.
Sperm DNA Integrity in Men Treated for Childhood Cancer
Authors: Romerius Patrik , Ståhl Olof , Moëll Christian , Relander Thomas , Cavallin-Ståhl Eva , Gustafsson Helen , Löfvander Thapper Kerstin , Jepson Katarina , Spanò Marcello , Wiebe Thomas , Lundberg Giwercman Yvonne , Giwercman Aleksander 
Published: June 2010

AbstractPurpose: It is not known whether childhood cancer and its treatment are associated with sperm DNA damage, which subsequently affects fertility and might be transmitted to the offspring. The aim of this study is to assess DNA fragmentation index (DFI) as an indicator of sperm DNA integrity in childhood cancer survivors (CCS), with treatment regimen taken into account.Experimental Design: In 99 CCS and 193 age-matched healthy controls, DFI was assessed by using sperm chromatin structure assay.Results: In the whole group of CCS, DFI was increased compared with the controls, with borderline statistical significance [mean difference, 1.8%; 95% confidence interval (95% CI), −0.0088%-3.7%]. Those treated with radiotherapy only (mean difference, 6.0%; 95% CI, 1.6–10%) or surgery only (mean difference, 2.9%; 95% CI, 0.083–5.8%) had statistically significantly higher DFI than the controls. The odds ratio (OR) for having DFI &gt;20%, which is associated with reduced fertility, was significantly increased in CCS compared with the control group (OR, 2.2; 95% CI, 1.1–4.4). For the radiotherapy-only group, the OR was even higher (OR, 4.9; 95% CI, 1.3–18). DFI was not associated with dose of scattered testicular irradiation or type of chemotherapy given.Conclusions: DFI was increased in CCS, with those treated with chemotherapy being the only exception. This sperm DNA impairment may be associated with the disease per se rather than due to the treatment, and may have negative consequences in terms of fertility and risk of transmission to the offspring. Clin Cancer Res; 16(15); 3843–50. ©2010 AACR.
Long-term Follow-up in Cancer Prevention Trials (It Ain't Over 'Til It's Over)
Authors: Cuzick Jack 
Published: June 2010

Abstract
The update of the Study of Tamoxifen and Raloxifene by Vogel et al. (beginning on p. 696 in this issue of the journal) highlights the overall importance of long-term follow-up of cancer prevention trials, which need long follow-up to fully determine agent risks and benefits. Biomarkers (e.g., reduced cervical intraepithelial neoplasia 3 after human papillomavirus vaccination) can provide an early indication of efficacy but almost never replace the cancer end point in determining the ultimate utility of an agent. Long follow-up is also important to fully determine preventive benefit, as illustrated by the tamoxifen trials, where only 60% as many treated women were needed to prevent one cancer at 10 years as at approximately 5 years, the time of the early reports. Cancer Prev Res; 3(6); 689–91. ©2010 AACR.
Changes in Events Alter How People Remember Recent Information
Authors: Swallow Khena M. , Barch Deanna M. , Head Denise , Maley Corey J. , Holder Derek , Zacks Jeffrey M. 
Published: June 2010

AbstractObservers spontaneously segment larger activities into smaller events. For example, “washing a car” might be segmented into “scrubbing,” “rinsing,” and “drying” the car. This process, called event segmentation, separates “what is happening now” from “what just happened.” In this study, we show that event segmentation predicts activity in the hippocampus when people access recent information. Participants watched narrative film and occasionally attempted to retrieve from memory objects that recently appeared in the film. The delay between object presentation and test was always 5 sec. Critically, for some of the objects, the event changed during the delay whereas for others the event continued. Using fMRI, we examined whether retrieval-related brain activity differed when the event changed during the delay. Brain regions involved in remembering past experiences over long periods, including the hippocampus, were more active during retrieval when the event changed during the delay. Thus, the way an object encountered just 5 sec ago is retrieved from memory appears to depend in part on what happened in those 5 sec. These data strongly suggest that the segmentation of ongoing activity into events is a control process that regulates when memory for events is updated.
Cardiorespiratory Fitness and the Flexible Modulation of Cognitive Control in Preadolescent Children
Authors: Pontifex Matthew B. , Raine Lauren B. , Johnson Christopher R. , Chaddock Laura , Voss Michelle W. , Cohen Neal J. , Kramer Arthur F. , Hillman Charles H. 
Published: June 2010

Abstract
The influence of cardiorespiratory fitness on the modulation of cognitive control was assessed in preadolescent children separated into higher- and lower-fit groups. Participants completed compatible and incompatible stimulus–response conditions of a modified flanker task, consisting of congruent and incongruent arrays, while ERPs and task performance were concurrently measured. Findings revealed decreased response accuracy for lower- relative to higher-fit participants with a selectively larger deficit in response to the incompatible stimulus–response condition, requiring the greatest amount of cognitive control. In contrast, higher-fit participants maintained response accuracy across stimulus–response compatibility conditions. Neuroelectric measures indicated that higher-fit, relative to lower-fit, participants exhibited global increases in P3 amplitude and shorter P3 latency, as well as greater modulation of P3 amplitude between the compatible and incompatible stimulus–response conditions. Similarly, higher-fit participants exhibited smaller error-related negativity (ERN) amplitudes in the compatible condition, and greater modulation of the ERN between the compatible and incompatible conditions, relative to lower-fit participants who exhibited large ERN amplitudes across both conditions. These findings suggest that lower-fit children may have more difficulty than higher-fit children in the flexible modulation of cognitive control processes to meet task demands.
Apples and Oranges: The Logic of the Early and Later Arabic Logicians
Authors: Spevack Aaron 
Published: June 2010

AbstractIn a recent article in Islamic Law and Society, Khaled El-Rouayheb proposed that opposition to logic was probably never the predominant view of Sunni Muslim scholars. El-Rouayheb also expressed doubt in the position of later scholars who argued that there existed two approaches to the study of logic, one whose permissibility was debated, and another whose permissibility was agreed upon. In response to El-Rouayheb, Mufti Ali argued in his own article that opposition to logic was the predominant view of Sunni Muslim scholars between the thirteenth and fifteenth centuries. In this article, I argue, pace Ali, that there is merit to the claim that neither opposition to, nor support for, logic achieved predominance, especially between the thirteenth and fifteenth centuries, even if favorable opinions came to be viewed as the soundest position in later centuries. I also argue, pace El-Rouayheb, that there is merit to the proposition that there are two distinct approaches to logic, one that mixes objectionable elements from Greek philosophy, and one that, in varying degrees, may have rid itself of these elements. Additionally, I argue that the thirteenth through fifteenth centuries may have marked a transitional period during which the two approaches became more distinct, although some jurists who ruled on logic did not always notice, or acknowledge, the distinction.