bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laboratory-Confirmed Case of Yaws in a 10-Year-Old Boy from the Republic of the Congo
Authors: Pillay Allan , Chen Cheng-Yen , Reynolds Mary G. , Mombouli Jean V. , Castro Arnold C. , Louvouezo Davy , Steiner Bret , Ballard Ronald C. 
Published: September 2011

ABSTRACT

We report a case of yaws in a patient with puritic cutaneous eruption who was initially suspected of infection with monkeypox. The diagnosis was established by real-time PCR and sequencing of specific treponemal DNA sequences. This is the first report describing the use of DNA sequencing to identify
Treponema pallidum
subsp.
pertenue
-specific sequences in a patient with active yaws.
Bartonella Species Bacteremia in Two Patients with Epithelioid Hemangioendothelioma
Authors: Mascarelli Patricia E. , Iredell Jonathan R. , Maggi Ricardo G. , Weinberg Guy , Breitschwerdt Edward B. 
Published: September 2011

ABSTRACTBartonella henselaeandB. koehleraebacteremia was documented in two epithelioid hemangioendothelioma patients andB. koehleraebacteremia in an asymptomatic partner of one of the patients. Considering the biology and clinically variable natural history of epithelioid hemangioendothelioma, these results suggest that chronicBartonellainfection could have a role in the development of this vascular neoplasm.Bartonellaspp. are known to induce vasoproliferative tumors in immunocompromised patients and may play a role in the development of epithelioid hemangioendothelioma in immunocompetent patients.
Stabilization of Influenza Virus Replication Intermediates Is Dependent on the RNA-Binding but Not the Homo-Oligomerization Activity of the Viral Nucleoprotein
Authors: Vreede Frank T. , Ng Andy Ka-Leung , Shaw Pang-Chui , Fodor Ervin 
Published: September 2011

ABSTRACT
The influenza virus nucleoprotein (NP) is believed to play a central role in directing a switch from RNA genome transcription to replication by the viral RNA polymerase. However, this role has recently been disputed with the proposal of alternative regulatory mechanisms. It has been suggested that the expression of viral polymerase and NP allows genome replication by stabilization of cRNA replication intermediates and complementary ribonucleoprotein (cRNP) assembly. Here, we demonstrate that the RNA-binding activity of NP is necessary for stabilization of cRNA, whereas, surprisingly, homo-oligomerization of NP is not essential. However, both RNA binding and homo-oligomerization activities are essential for genome replication.
The Reovirus σ1s Protein Is a Determinant of Hematogenous but Not Neural Virus Dissemination in Mice
Authors: Boehme Karl W. , Frierson Johnna M. , Konopka Jennifer L. , Kobayashi Takeshi , Dermody Terence S. 
Published: September 2011

ABSTRACTNonstructural protein σ1s is a critical determinant of hematogenous dissemination by type 1 reoviruses, which reach the central nervous system (CNS) by a strictly blood-borne route. However, it is not known whether σ1s contributes to neuropathogenesis of type 3 reoviruses, which disseminate by both vascular and neural pathways. Using isogenic type 3 viruses that vary only in σ1s expression, we observed that mice survived at a higher frequency following hind-limb inoculation with σ1s-null virus than when inoculated with wild-type virus. This finding suggests that σ1s is essential for reovirus virulence when inoculated at a site that requires systemic spread to cause disease. Wild-type and σ1s-null viruses produced comparable titers in the spinal cord, suggesting that σ1s is dispensable for invasion of the CNS. Although the two viruses ultimately achieved similar peak titers in the brain, loads of wild-type virus were substantially greater than those of the σ1s-null mutant at early times after inoculation. In contrast, wild-type virus produced substantially higher titers than the σ1s-null virus in peripheral organs to which reovirus spreads via the blood, including the heart, intestine, liver, and spleen. Concordantly, viral titers in the blood were higher following infection with wild-type virus than following infection with the σ1s-null mutant. These results suggest that differences in viral brain titers at early time points postinfection are due to limited virus delivery to the brain by hematogenous pathways. Transection of the sciatic nerve prior to hind-limb inoculation diminished viral spread to the spinal cord. However, wild-type virus retained the capacity to disseminate to the brain following sciatic nerve transection, indicating that wild-type reovirus can spread to the brain by the blood. Together, these results indicate that σ1s is not required for reovirus spread by neural mechanisms. Instead, σ1s mediates hematogenous dissemination within the infected host, which is required for full reovirus neurovirulence.
The SI Strain of Measles Virus Derived from a Patient with Subacute Sclerosing Panencephalitis Possesses Typical Genome Alterations and Unique Amino Acid Changes That Modulate Receptor Specificity and Reduce Membrane Fusion Activity
Authors: Seki Fumio , Yamada Kentaro , Nakatsu Yuichiro , Okamura Koji , Yanagi Yusuke , Nakayama Tetsuo , Komase Katsuhiro , Takeda Makoto 
Published: September 2011

ABSTRACT
Subacute sclerosing panencephalitis (SSPE) is a fatal sequela associated with measles and is caused by persistent infection of the brain with measles virus (MV). The SI strain was isolated in 1976 from a patient with SSPE and shows neurovirulence in animals. Genome nucleotide sequence analyses showed that the SI strain genome possesses typical genome alterations for SSPE-derived strains, namely, accumulated amino acid substitutions in the M protein and cytoplasmic tail truncation of the F protein. Through the establishment of an efficient reverse genetics system, a recombinant SI strain expressing a green fluorescent protein (rSI-AcGFP) was generated. The infection of various cell types with rSI-AcGFP was evaluated by fluorescence microscopy. rSI-AcGFP exhibited limited syncytium-forming activity and spread poorly in cells. Analyses using a recombinant MV possessing a chimeric genome between those of the SI strain and a wild-type MV strain indicated that the membrane-associated protein genes (M, F, and H) were responsible for the altered growth phenotype of the SI strain. Functional analyses of viral glycoproteins showed that the F protein of the SI strain exhibited reduced fusion activity because of an E300G substitution and that the H protein of the SI strain used CD46 efficiently but used the original MV receptors on immune and epithelial cells poorly because of L482F, S546G, and F555L substitutions. The data obtained in the present study provide a new platform for analyses of SSPE-derived strains as well as a clear example of an SSPE-derived strain that exhibits altered receptor specificity and limited fusion activity.
Sequences in Gibbon Ape Leukemia Virus Envelope That Confer Sensitivity to HIV-1 Accessory Protein Vpu
Authors: Janaka Sanath Kumar , Lucas Tiffany M. , Johnson Marc C. 
Published: September 2011

ABSTRACT
HIV-1 efficiently forms pseudotyped particles with many gammaretrovirus glycoproteins, such as Friend murine leukemia virus (F-MLV) Env, but not with the related gibbon ape leukemia virus (GaLV) Env or with a chimeric F-MLV Env with a GaLV cytoplasmic tail domain (CTD). This incompatibility is modulated by the HIV-1 accessory protein Vpu. Because the GaLV Env CTD does not resemble tetherin or CD4, the well-studied targets of Vpu, we sought to characterize the modular sequence in the GaLV Env CTD required for this restriction in the presence of Vpu. Using a systematic mutagenesis scan, we determined that the motif that makes GaLV Env sensitive to Vpu is INxxIxxVKxxVxRxK. This region in the CTD of GaLV Env is predicted to form a helix. Mutations in the CTD that would break this helix abolish sensitivity to Vpu. Although many of these positions can be replaced with amino acids with similar biophysical properties without disrupting the Vpu sensitivity, the final lysine residue is required. This Vpu sensitivity sequence appears to be modular, as the unrelated Rous sarcoma virus (RSV) Env can be made Vpu sensitive by replacing its CTD with the GaLV Env CTD. In addition, F-MLV Env can be made Vpu sensitive by mutating two amino acids in its cytoplasmic tail to make it resemble more closely the Vpu sensitivity motif. Surprisingly, the core components of this Vpu sensitivity sequence are also present in the host surface protein CD4, which is also targeted by Vpu through its CTD.
Comparative Analysis of Poxvirus Orthologues of the Vaccinia Virus E3 Protein: Modulation of Protein Kinase R Activity, Cytokine Responses, and Virus Pathogenicity
Authors: Myskiw Chad , Arsenio Janilyn , Hammett Craig , van Bruggen Rebekah , Deschambault Yvon , Beausoleil Nicole , Babiuk Shawn , Cao Jingxin 
Published: September 2011

ABSTRACT

Poxviruses are important human and animal pathogens that have evolved elaborate strategies for antagonizing host innate and adaptive immunity. The E3 protein of vaccinia virus, the prototypic member of the orthopoxviruses, functions as an inhibitor of innate immune signaling and is essential for vaccinia virus replication in vivo and in many human cell culture systems. However, the function of orthologues of E3 expressed by poxviruses of other genera with different host specificity remains largely unknown. In the present study, we characterized the E3 orthologues from sheeppox virus, yaba monkey tumor virus, swinepox virus, and myxoma virus for their ability to modulate protein kinase R (PKR) function, cytokine responses and virus pathogenicity. We found that the E3 orthologues of myxoma virus and swinepox virus could suppress PKR activation and interferon (IFN)-induced antiviral activities and restore the host range function of E3 in HeLa cells. In contrast, the E3 orthologues from sheeppox virus and yaba monkey tumor virus were unable to inhibit PKR activation. While the sheeppox orthologue was unable to restore the host range function of E3, the yaba monkey tumor virus orthologue partially restored E3-deficient vaccinia virus replication in HeLa cells, correlated with its ability to suppress IFN-induced antiviral activities. Moreover, poxvirus E3 orthologues show varying ability to inhibit the induction of antiviral and proinflammatory cytokines. Despite these
in vitro
results, none of the E3 orthologues tested was capable of restoring pathogenicity to E3-deficient vaccinia virus
in vivo
.
Analysis of Influenza Virus Hemagglutinin Receptor Binding Mutants with Limited Receptor Recognition Properties and Conditional Replication Characteristics
Authors: Bradley Konrad C. , Galloway Summer E. , Lasanajak Yi , Song Xuezheng , Heimburg-Molinaro Jamie , Yu Hai , Chen Xi , Talekar Ganesh R. , Smith David F. , Cummings Richard D. , Steinhauer David A. 
Published: September 2011

ABSTRACT
To examine the range of selective processes that potentially operate when poorly binding influenza viruses adapt to replicate more efficiently in alternative environments, we passaged a virus containing an attenuating mutation in the hemagglutinin (HA) receptor binding site in mice and characterized the resulting mutants with respect to the structural locations of mutations selected, the replication phenotypes of the viruses, and their binding properties on glycan microarrays. The initial attenuated virus had a tyrosine-to-phenylalanine mutation at HA1 position 98 (Y98F), located in the receptor binding pocket, but viruses that were selected contained second-site pseudoreversion mutations in various structural locations that revealed a range of molecular mechanisms for modulating receptor binding that go beyond the scope that is generally mapped using receptor specificity mutants. A comparison of virus titers in the mouse respiratory tract versus MDCK cells in culture showed that the mutants displayed distinctive replication properties depending on the system, but all were less attenuated in mice than the Y98F virus. An analysis of receptor binding properties confirmed that the initial Y98F virus bound poorly to several different species of erythrocytes, while all mutants reacquired various degrees of hemagglutination activity. Interestingly, both the Y98F virus and pseudoreversion mutants were shown to bind very inefficiently to standard glycan microarrays containing an abundance of binding substrates for most influenza viruses that have been characterized to date, provided by the Consortium for Functional Glycomics. The viruses were also examined on a recently developed microarray containing glycans terminating in sialic acid derivatives, and limited binding to a potentially interesting subset of glycans was revealed. The results are discussed with respect to mechanisms for HA-mediated receptor binding, as well as regarding the species of molecules that may act as receptors for influenza virus on host cell surfaces.
The Interaction between Bamboo Mosaic Virus Replication Protein and Coat Protein Is Critical for Virus Movement in Plant Hosts
Authors: Lee Cheng-Cheng , Ho Yuan-Ning , Hu Rei-Hsing , Yen Yu-Ting , Wang Zheng-Cheng , Lee Ya-Chien , Hsu Yau-Heiu , Meng Menghsiao 
Published: September 2011

ABSTRACT

Bamboo mosaic virus
(BaMV) is a positive-sense RNA virus belonging to the genus
Potexvirus
. Open reading frame 1 (ORF1) encodes the viral replication protein that consists of a capping enzyme domain, a helicase-like domain (HLD), and an RNA-dependent RNA polymerase domain from the N to C terminus. ORF5 encodes the viral coat protein (CP) required for genome encapsidation and the virus movement in plants. In this study, application of a yeast-two hybrid assay detected an interaction between the viral HLD and CP. However, the interaction did not affect the NTPase activity of the HLD. To identify the critical amino acids of CP interacting with the HLD, a random mutational library of CP was created using error-prone PCR, and the mutations adversely affecting the interaction were screened by a bacterial two-hybrid system. As a result, the mutations A209G and N210S in CP were found to weaken the interaction. To determine the significance of the interaction, the mutations were introduced into a BaMV infectious clone, and the mutational effects on viral replication, movement, and genome encapsidation were investigated. There was no effect on accumulations of BaMV CP and genomic RNAs within protoplasts; however, the virus cell-to-cell movement in plants was restricted. Sequence alignment revealed that A209 of BaMV CP is conserved in many potexviruses. Mutation of the corresponding residue in
Foxtail mosaic virus
CP also reduced the viral HLD-CP interaction and restricted the virus movement, suggesting that interaction between CP and a widely conserved HLD in the potexviral replication protein is crucial for viral trafficking through plasmodesmata.
Solution Properties of Murine Leukemia Virus Gag Protein: Differences from HIV-1 Gag
Authors: Datta Siddhartha A. K. , Zuo Xiaobing , Clark Patrick K. , Campbell Stephen J. , Wang Yun-Xing , Rein Alan 
Published: September 2011

ABSTRACT
Immature retrovirus particles are assembled from the multidomain Gag protein. In these particles, the Gag proteins are arranged radially as elongated rods. We have previously characterized the properties of HIV-1 Gag in solution. In the absence of nucleic acid, HIV-1 Gag displays moderately weak interprotein interactions, existing in monomer-dimer equilibrium. Neutron scattering and hydrodynamic studies suggest that the protein is compact, and biochemical studies indicate that the two ends can approach close in three-dimensional space, implying the need for a significant conformational change during assembly. We now describe the properties of the Gag protein of Moloney murine leukemia virus (MLV), a gammaretrovirus. We found that this protein is very different from HIV-1 Gag: it has much weaker protein-protein interaction and is predominantly monomeric in solution. This has allowed us to study the protein by small-angle X-ray scattering and to build a low-resolution molecular envelope for the protein. We found that MLV Gag is extended in solution, with an axial ratio of ∼7, comparable to its dimensions in immature particles. Mutational analysis suggests that runs of prolines in its matrix and p12 domains and the highly charged stretch at the C terminus of its capsid domain all contribute to this extended conformation. These differences between MLV Gag and HIV-1 Gag and their implications for retroviral assembly are discussed.
013 Resuscitation feedback and targeted education improves quality of pre-hospital resuscitation in Scotland
Authors: Clarke S , Lyon R M , Milligan D J , Clegg G R 
Published: September 2011

Objectives and BackgroundsOut-of-hospital cardiac arrest is a leading cause of mortality and neurological morbidity in the UK. Cardiopulmonary resuscitation is vital to maintaining cerebral and cardiac perfusion until return of spontaneous circulation. Recent studies have demonstrated the adverse physiological consequences of poor resuscitation technique and that quality of Cardiopulmonary resuscitation is a critical determinant of outcome. Analysis of the defibrillator transthoracic impedance (TTI) trace gives an objective measure of pre-hospital resuscitation quality. This study aims to analyse the impact of targeted resuscitation feedback and training on quality of pre-hospital resuscitation.MethodsSingle centre, prospective cohort study over 13 months (1st December 2009–31st December 2010). Modems were fitted to the defibrillators on vehicles from Edinburgh City ambulance station (n=40). Resuscitation events were collected by telemetry and analysed. Outcome measures were: resuscitation time spent performing chest compressions, compression rate, hands-off time required to deliver a shock and use of automatic or manual defibrillator mode. Baseline data were gathered over a 3-month period. Monthly resuscitation classes and personalised written feedback following each resuscitation attempt were then introduced for 6 months. Resuscitation quality was again measured and compared to baseline data.ResultsAnalysis of 111 downloads showed hands-on-chest time improved significantly following feedback and targeted resuscitation training (73.0% vs 79.3%, p=0.007). Compression rate was unchanged (Abstract 013 figures 1 and 2). There was a significant reduction in median time-to-shock interval from 20.25 s (IQR 15.50–25.50 s) to 13.45 s (IQR 2.25–22.00 s) (p=0.006). Use of automatic rhythm recognition fell from 50% to 28.6% (p=0.03).Abstract 013 Figure 1Frequency histogram showing the distribution of compression rates around the “ideal” 90–110/min (2005 Guidelines: shaded area) during the baseline data collection period.Abstract 013 Figure 2Frequency histogram showing the distribution of compression rates around the “ideal” 90–110/min (2005 Guidelines: shaded area) following implementation of feedback and resuscitation training.ConclusionsTTI trace analysis following Out-of-hospital cardiac arrest allows objective evaluation of resuscitation quality. Targeted training and feedback improves the quality of pre-hospital resuscitation. Further studies are required to establish improvement in survival as a result of this approach.
031 Delivering safety net advice and the Emergency Department Clinical Quality Indicator of unplanned re-attendance in children
Authors: Roland D , Geliot T , Patel A 
Published: September 2011

Objectives and BackgroundA Department of Health study has shown parents of children presenting with fever who did not receive safety net advice were more likely to unnecessarily re-attend. This work aimed to improve the proportion of safety net advice given by junior doctors at the outset of their attachment. In 2009, an audit of feverish children who presented to our Emergency Department found the number of junior doctors providing safety net advice to parents fell from 70.9% in July to 55.9% when a new cohort commenced in August.MethodsA key slide set was introduced into the paediatric induction lecture (given during the Emergency Department's internal programme) regarding safety net advice in August 2010.ResultsFollowing this awareness campaign, an audit involving 457 case notes revealed safety net advice increased significantly from 76.0% in July 2010 to 89.5% in the August cohort. In 2009 there were 41 medically related re-attendances in July (39.0% subsequently admitted) and 48 in August (41.7% admitted). These “return to be admitted” rates were not significantly different (Z value 0.037, p>0.05). In 2010 there were 50 medically related representations in July (40.0% admitted) and 54 in August (27.8% admitted). These “return to be admitted” rates were not significantly different (Z value 1.11, p>0.05). In children aged 16 and over the total number of re-attendees increased from 6.5% to 7.2% between July and August 2010 with the August result significantly higher than the year total (Z value 2.655, p<0.01) although August had the highest re-attendance amount of the year. In children under 16 re-attendees fell from 3.9% to 3.6% between July and August with the August result not being significantly different from the year total (Z value 1.502, p>0.05).ConclusionThe provision of improved safety net advice did not increase the Clinical Quality Indicator of unplanned re-attendance. Induction programmes have an important role to play in promoting evidence-based practice and improving quality.
009 No more “admit for 12 h trop”? Cardiac markers point of care testing in patients with suspected low to moderate risk ACS
Authors: Robinson D , Choudhry T , Nisar S , Barker M , Lee G 
Published: September 2011

Objectives and BackgroundsCurrent diagnostic strategies using cardiac markers in the assessment of suspected acute coronary syndrome (ACS) involve the measurement of serum troponin 10–12 h after the onset of chest pain. We evaluated the potential impact of a multimarker strategy using point of care (POC) measurement of myoglobin, creatine kinase (CK)-MB and troponin I to exclude MI in ≤90 min.MethodsPatients presenting to the Emergency Department with suspected ACS with non-diagnostic ECGs were included. We measured myoglobin, CK-MB and troponin I with a POC device at presentation and at 90 min. Standard laboratory testing of troponin I was performed at 12 h. Sensitivity, specificity and likelihood ratios for the POC triple cardiac marker strategy were calculated. We also calculated time to decision point for POC testing vs laboratory testing.ResultsComplete data were available for 109 patients. 73 patients had negative POC testing and normal laboratory troponin. POC markers were positive in 36 patients, of which 19 had positive 12 h laboratory troponin I. Sensitivity of POC cardiac markers was 100% (95% CI 0.79% to 1.0%), specificity 81% (95% CI 0.71% to 0.88%), negative likelihood ratio <0.001 and positive likelihood ratio 5.29. Mean time to decision point was 700 min earlier for POC testing vs laboratory troponin measurement. We estimate that implementation of the triple cardiac markers POC pathway in our institution would save 3 beds per day.ConclusionsTriple cardiac marker POC testing at 90 min can be used to reliably exclude acute myocardial infarction in patients with low to moderate risk ACS, and has the potential to reduce inpatient medical bed occupancy.