bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Vaccinia Virus-Encoded Bcl-2 Homologues Do Not Act as Direct Bax Inhibitors
Authors: Postigo Antonio , Way Michael 
Published: October 2011

ABSTRACT

Many viruses, including members of several poxvirus genera, encode inhibitors that block apoptosis by simultaneously binding the proapoptotic Bcl-2 proteins Bak and Bax. The
Orthopoxvirus
vaccinia virus encodes the Bcl-2-like F1 protein, which sequesters Bak but not Bax. However, N1, a potent virulence factor, is reported to be antiapoptotic and to interact with Bax. Here we investigated whether vaccinia virus inhibits Bak/Bax-dependent apoptosis via the cooperative action of F1 and N1. We found that Western Reserve (WR) and ΔN1L viruses inhibited drug- and infection-induced apoptosis equally. Meanwhile, infections with ΔF1L or ΔN1L/F1L virus resulted in similar levels of Bax activation and apoptosis. Outside the context of infection, N1 did not block drug- or Bax-induced cell death or interact with Bax. In addition to F1 and N1, vaccinia virus encodes further structural homologs of Bcl-2 proteins that are conserved in orthopoxviruses, including A46, A52, B14, C1, C6, C16/B22, K7, and N2. However, we found that these do not associate with Bax or inhibit drug-induced cell death. Based on our findings that N1 is not an antiapoptotic protein, we propose that the F1 orthologs represent the only orthopoxvirus Bcl-2 homolog to directly inhibit the Bak/Bax checkpoint.
High-Resolution Profiling and Analysis of Viral and Host Small RNAs during Human Cytomegalovirus Infection
Authors: Stark Thomas J. , Arnold Justin D. , Spector Deborah H. , Yeo Gene W. 
Published: October 2011

ABSTRACTHuman cytomegalovirus (HCMV) contributes its own set of microRNAs (miRNAs) during lytic infection of cells, likely fine-tuning conditions important for viral replication. To enhance our understanding of this component of the HCMV-host transcriptome, we have conducted deep-sequencing analysis of small RNAs (smRNA-seq) from infected human fibroblast cells. We found that HCMV-encoded miRNAs accumulate to ∼20% of the total smRNA population at late stages of infection, and our analysis led to improvements in viral miRNA annotations and identification of two novel HCMV miRNAs, miR-US22 and miR-US33as. Both of these miRNAs were capable of functionally repressing synthetic targets in transient transfection experiments. Additionally, through cross-linking and immunoprecipitation (CLIP) of Argonaute (Ago)-bound RNAs from infected cells, followed by high-throughput sequencing, we have obtained direct evidence for incorporation of all HCMV miRNAs into the endogenous host silencing machinery. Surprisingly, three HCMV miRNA precursors exhibited differential incorporation of their mature miRNA arms between Ago2 and Ago1 complexes. Host miRNA abundances were also affected by HCMV infection, with significant upregulation observed for an miRNA cluster containing miR-96, miR-182, and miR-183. In addition to miRNAs, we also identified novel forms of virus-derived smRNAs, revealing greater complexity within the smRNA population during HCMV infection.
Complete Genome Sequence of a Coxsackievirus A22 Strain in Hong Kong Reveals a Natural Intratypic Recombination Event
Authors: Yip Cyril C. Y. , Lau Susanna K. P. , Woo Patrick C. Y. , Chan Kwok-Hung , Yuen Kwok-Yung 
Published: October 2011

ABSTRACT

Coxsackievirus A22 (CVA22) belongs to the species human enterovirus C in the
Picornaviridae
family. We report the first complete genome sequence of CVA22 with natural intratypic recombination between CVA22 prototype strain Chulman and CVA22 strain ban99-10427, identified in the stool of a patient in Hong Kong.
Analysis of the Interaction between the Essential Herpes Simplex Virus 1 Tegument Proteins VP16 and VP1/2
Authors: Svobodova Stanislava , Bell Susanne , Crump Colin M. 
Published: October 2011

ABSTRACT

The incorporation of tegument proteins into the herpes simplex virus 1 (HSV-1) virion during virion assembly is thought to be a complex, multistage process occurring via numerous interactions between the tegument and the capsid, within the tegument, and between the tegument and the envelope. Here, we set out to examine if the direct interaction between two essential tegument proteins VP1/2 and VP16 is required for connecting the inner tegument with the outer tegument. By using glutathione
S
-transferase (GST) pulldowns, we identified an essential role of lysine 343 in VP16, mutation of which to a neutral amino acid abrogated the interaction between VP1/2 and VP16. When the K343A substitution was inserted into the gene encoding VP16 (UL48) of the viral genome, HSV-1 replicated successfully although its growth was delayed, and final titers were reduced compared to titers of wild-type virus. Surprisingly, the mutated VP16 was incorporated into virions at levels similar to those of wild-type VP16. However, the analysis of VP16 on cytoplasmic capsids by fluorescence microscopy showed that VP16 associated with cytoplasmic capsids less efficiently when the VP16-VP1/2 interaction was inhibited. This implies that the direct interaction between VP1/2 and VP16 is important for the efficiency/timing of viral assembly but is not essential for HSV-1 replication in cell culture. These data also support the notion that the incorporation of tegument proteins into the herpesviruses is a very complex process with significant redundancy.
The Activity Spectrum of Vif from Multiple HIV-1 Subtypes against APOBEC3G, APOBEC3F, and APOBEC3H
Authors: Binka Mawuena , Ooms Marcel , Steward Myeika , Simon Viviana 
Published: October 2011

ABSTRACT

The APOBEC3 family comprises seven cytidine deaminases (APOBEC3A [A3A] to A3H), which are expressed to various degrees in HIV-1 susceptible cells. The HIV-1 Vif protein counteracts APOBEC3 restriction by mediating its degradation by the proteasome. We hypothesized that Vif proteins from various HIV-1 subtypes differ in their abilities to counteract different APOBEC3 proteins. Seventeen Vif alleles from seven HIV-1 subtypes were tested for their abilities to degrade and counteract A3G, A3F, and A3H haplotype II (hapII). We show that most Vif alleles neutralize A3G and A3F efficiently but display differences with respect to the inhibition of A3H hapII. The majority of non-subtype B Vif alleles tested presented some activity against A3H hapII, with two subtype F Vif variants being highly effective in counteracting A3H hapII. The residues required for activity were mapped to two residues in the amino-terminal region of Vif (positions 39F and 48H). Coimmunoprecipitations showed that these two amino acids were necessary for association of Vif with A3H hapII. These findings suggest that the A3H hapII binding site in Vif is distinct from the regions important for A3G and A3F recognition and that it requires specific amino acids at positions 39 and 48. The differential Vif activity spectra, especially against A3H hapII, suggest adaptation to APOBEC3 repertoires representative of different human ancestries. Phenotypic assessment of anti-APOBEC3 activity of Vif variants against several cytidine deaminases will help reveal the requirement for successful replication
in vivo
and ultimately point to interventions targeting the Vif-APOBEC3 interface.
Amino Acid Changes in Hemagglutinin Contribute to the Replication of Oseltamivir-Resistant H1N1 Influenza Viruses
Authors: Ginting Teridah Ernala , Shinya Kyoko , Kyan Yukihiro , Makino Akiko , Matsumoto Naomi , Kaneda Satoko , Kawaoka Yoshihiro 
Published: October 2011

ABSTRACTOseltamivir-resistant H1N1 influenza viruses emerged in 2007 to 2008 and have subsequently circulated widely. However, prior to 2007 to 2008, viruses possessing the neuraminidase (NA) H274Y mutation, which confers oseltamivir resistance, generally had low growth capability. NA mutations that compensate for the deleterious effect of the NA H274Y mutation have since been identified. Given the importance of the functional balance between hemagglutinin (HA) and NA, we focused on amino acid changes in HA. Reverse genetic analysis showed that a mutation at residue 82, 141, or 189 of the HA protein promotes virus replication in the presence of the NA H274Y mutation. Our findings thus identify HA mutations that contributed to the replacement of the oseltamivir-sensitive viruses of 2007 to 2008.
Mutations at the Base of the Icosahedral Five-Fold Cylinders of Minute Virus of Mice Induce 3′-to-5′ Genome Uncoating and Critically Impair Entry Functions
Authors: Cotmore Susan F. , Tattersall Peter 
Published: October 2011

ABSTRACT

The linear single-stranded DNA genome of minute virus of mice can be ejected, in a 3′-to-5′ direction, via a cation-linked uncoating reaction that leaves the 5′ end of the DNA firmly complexed with its otherwise intact protein capsid. Here we compare the phenotypes of four mutants, L172T, V40A, N149A, and N170A, which perturb the base of cylinders surrounding the icosahedral 5-fold axes of the virus, and show that these structures are strongly implicated in 3′-to-5′ release. Although noninfectious at 37°C, all mutants were viable at 32°C, showed a temperature-sensitive cell entry defect, and, after proteolysis of externalized VP2 N termini, were unable to protect the VP1 domain, which is essential for bilayer penetration. Mutant virus yields from multiple-round infections were low and were characterized by the accumulation of virions containing subgenomic DNAs of specific sizes. In V40A, these derived exclusively from the 5′ end of the genome, indicative of 3′-to-5′ uncoating, while L172T, the most impaired mutant, had long subgenomic DNAs originating from both termini, suggesting additional packaging portal defects. Compared to the wild type, genome release
in vitro
following cation depletion was enhanced for all mutants, while only L172T released DNA, in both directions, without cation depletion following proteolysis at 37°C. Analysis of progeny from single-round infections showed that uncoating did not occur during virion assembly, release, or extraction. However, unlike the wild type, the V40A mutant extensively uncoated during cell entry, indicating that the V40-L172 interaction restrains an uncoating trigger mechanism within the endosomal compartment.
Generation of HIV Latency in Humanized BLT Mice
Authors: Denton Paul W. , Olesen Rikke , Choudhary Shailesh K. , Archin Nancy M. , Wahl Angela , Swanson Michael D. , Chateau Morgan , Nochi Tomonori , Krisko John F. , Spagnuolo Rae Ann , Margolis David M. , Garcia J. Victor 
Published: October 2011

ABSTRACT

Here we demonstrate that a combination of tenofovir, emtricitabine, and raltegravir effectively suppresses peripheral and systemic HIV replication in humanized BLT mice. We also demonstrate that antiretroviral therapy (ART)-treated humanized BLT mice harbor latently infected resting human CD4
+
T cells that can be induced
ex vivo
to produce HIV. We observed that the levels of infected resting human CD4
+
T cells present in BLT mice are within the range of those observed circulating in patients undergoing suppressive ART. These results demonstrate the potential of humanized BLT mice as an attractive model for testing the
in vivo
efficacy of novel HIV eradication strategies.
Do nurse and patient injuries share common antecedents? An analysis of associations with safety climate and working conditions
Authors: Taylor Jennifer A , Dominici Francesca , Agnew Jacqueline , Gerwin Daniel , Morlock Laura , Miller Marlene R 
Published: October 2011

BackgroundSafety climate and nurses' working conditions may have an impact on both patient outcomes and nurse occupational health, but these outcomes have rarely been examined concurrently.ObjectiveTo examine the association of unit-level safety climate and specific nurse working conditions with injury outcomes for both nurses and patients in a single hospital.Research designA cross-sectional study was conducted using nursing-unit level and individual-level data at an urban, level-one trauma centre in the USA. Multilevel logistic regressions were used to examine associations among injury outcomes, safety climate and working conditions on 29 nursing units, including a total of 723 nurses and 28 876 discharges.MeasuresSafety climate was measured in 2004 using the Safety Attitudes Questionnaire (SAQ). Working conditions included registered nursing hours per patient day (RNHPPD) and unit turnover. Patient injuries included 290 falls, 167 pulmonary embolism/deep vein thrombosis (PE/DVT), and 105 decubitus ulcers. Nurse injury was defined as a reported needle-stick, splash, slip, trip, or fall (n=78). Working conditions and outcomes were measured in 2005.ResultsThe study found a negative association between two SAQ domains, Safety and Teamwork, with the odds of both decubitus ulcers and nurse injury. RNHPPD showed a negative association with patient falls and decubitus ulcers. Unit turnover was positively associated with nurse injury and PE/DVT, but negatively associated with falls and decubitus ulcers.ConclusionsSafety climate was associated with both patient and nurse injuries, suggesting that patient and nurse safety may actually be linked outcomes. The findings also indicate that increased unit turnover should be considered a risk factor for nurse and patient injuries.
What drives hospital performance? The impact of comparative outcome evaluation of patients admitted for hip fracture in two Italian regions
Authors: Pinnarelli Luigi , Nuti Sabina , Sorge Chiara , Davoli Marina , Fusco Danilo , Agabiti Nera , Vainieri Milena , Perucci Carlo A 
Published: October 2011

BackgroundFrom 2006 to 2007 Lazio and Tuscany, two Italian regions, released data about hospital performance and implemented strategic programmes aimed at improving the quality of hospital care. Furthermore, different pay-for-performance systems were introduced: the hospital's performance determined the DRG (Diagnosis-Related Group) reimbursement rate for Lazio providers while in Tuscany the chief executive officer's compensation was linked to the hospital's performance. The authors evaluated the impact of the Lazio and Tuscany programmes on quality of healthcare for orthopaedic patients compared with other Italian regions.MethodsThe proportion of older patients admitted with hip fractures who had surgery within 48 h and the median waiting time for surgical treatment of fractures of the tibia or fibula were estimated separately for Lazio, Tuscany and other Italian regions for two periods: 2006–2007 and 2008–2009. Risk-adjusted proportions were obtained using the direct standardisation method and a multivariate logistic regression was performed taking into account age, gender and comorbidity status.ResultsThe proportion of hip operations performed within 48 h was increased by 34% for Lazio (p<0.001) and 46% for Tuscany (p<0.001) and reduced by 3% in other Italian regions (p<0.001). To assess for possible adverse consequences, such as increased waiting times for other orthopaedic procedures, the authors monitored time to surgery for tibia or fibula fractures. There were no significant differences in the median time to surgery for tibia or fibula fractures between the two periods.ConclusionsThe Lazio and Tuscany programmes appeared to have a positive impact on quality of care for older patients admitted with hip fracture without having a negative impact on other orthopaedic interventions. The results highlight the need for continuous quality improvement by repeating the evaluation process and by combining the performance system with a management strategy.
Predictive factors of bacteraemia in low-risk patients with febrile neutropenia
Authors: Ahn Shin , Lee Yoon-Seon , Chun Yeon Hee , Lim Kyung Soo , Kim Won , Lee Jae-Lyun 
Published: October 2011

PurposeThe authors intended to determine the predictive factors of bacteraemia in low-risk febrile neutropenia (FN) classified by the Multinational Association for Supportive Care in Cancer Risk Index score.MethodsFN episodes managed in an emergency department from June 2009 to May 2010 were included. Clinical and laboratory features including procalcitonin (PCT) and C reactive protein (CRP) were retrospectively analysed.ResultsOf the total 285 episodes, 243 (85.3%) were classified as low risk. In this group, 19 (7.8%) had bacteraemia. There was a significant difference (p<0.05) in age, respiration rate ≥24 (36.8% vs 7.6%), Eastern Cooperative Oncology Group performance status (PS) ≥2 (42.1% vs 11.6%), platelet counts (107.0±42.4 vs 131.8±73.7 ×103/mm3), serum aspartate aminotransferase (42.3±30.7 vs 28.7±17.4 IU/litre) and blood urea nitrogen (19.6±9.8 vs 11.6± 8.6 mg/dl) between episodes with and without bacteraemia. PCT ≥0.5 ng/ml and CRP ≥10 mg/dl had higher rates of bacteraemia than PCT <0.5 ng/ml (28.2% vs 3.9%, p<0.001) and CRP <10 mg/dl (13.9% vs 5.3%, p=0.022) did. On multivariate analysis, PCT ≥0.5 ng/ml (OR 4.7, 95% CI 1.38 to 16.29), respiration rate ≥24 (OR 4.1, 95% CI 1.20 to 13.63) and Eastern Cooperative Oncology Group PS ≥2 (OR 3.2, 95% CI 1.02 to 10.10) were predictive of bacteraemia in the low-risk group.ConclusionPCT, tachypnoea and PS were predictive of bacteraemia in the low-risk patients with FN. If the patient has high probability of bacteraemia, the patient could benefit from parenteral antibiotic treatment while awaiting the blood culture results.
Causes of pulmonary granulomas: a retrospective study of 500 cases from seven countries
Authors: Mukhopadhyay Sanjay , Farver Carol F , Vaszar Laszlo T , Dempsey Owen J , Popper Helmut H , Mani Haresh , Capelozzi Vera L , Fukuoka Junya , Kerr Keith M , Zeren E Handan , Iyer Venkateswaran K , Tanaka Tomonori , Narde Ivy , Nomikos Angheliki , Gumurdulu Derya , Arava Sudheer , Zander Dani S , Tazelaar Henry D 
Published: October 2011

BackgroundThe frequencies of various causes of pulmonary granulomas in pathological material are unknown, as is the influence of geographical location on aetiology. The aim of this study was to identify the causes of pulmonary granulomas in pathological specimens, to define their frequencies, and to determine whether these causes vary by geographical location.Methods500 lung biopsies and resections containing granulomas were reviewed retrospectively by expert pulmonary pathologists from 10 institutions in seven countries. Fifty consecutive cases from each location were assigned a diagnosis based on histological features and available clinical/microbiological data.ResultsA specific cause was identified in 58% of cases (290/500), most commonly sarcoidosis (136, 27%) and mycobacterial or fungal infections (125, 25%). Mycobacteria were identified in 19% of cases outside the USA versus 8% within the USA. In contrast, fungi accounted for 19% cases in the USA versus 4% in other locations. Fungi were mostly detected by histology, whereas most mycobacteria were identified in cultures. In 42% of cases (210/500) an aetiology could not be determined.ConclusionsAcross several geographical settings, sarcoidosis and infections are the most common causes of pulmonary granulomas diagnosed in pathological specimens. Fungi are more commonly identified than mycobacteria in the USA, whereas the reverse is true in other countries. A definite aetiology cannot be demonstrated in more than a third of all cases of pulmonary granulomas, even after histological examination. These findings highlight the need to submit material for histology as well as cultures in all cases in which granulomatous disease enters the differential diagnosis.
Clinicopathological and molecular study of penile melanoma
Authors: Oxley J D , Corbishley C , Down L , Watkin N , Dickerson D , Wong N A C S 
Published: October 2011

AimsTo examine the clinicopathological features of a series of penile melanomas and screen for mutations in theBRAFandKITgenes, which are seen in melanomas from other sites.Methods and results12 patients with penile melanoma were identified over a 10-year period in two supra-regional networks in the UK. The 2- and 5-year survival was 61% and 20%, respectively. Half the patients had lymph node involvement at presentation; this was a poor prognostic indicator.KITexons 11, 13, 17 and 18, andBRAFcodons 600 and 601 were analysed for mutations by Sanger sequencing and pyrosequencing, respectively. None of the tumours showed eitherKITmutations or theBRAFV600E mutation.ConclusionPenile melanomas are extremely rare and have a similar prognosis to melanomas elsewhere, but they often present late, leading to a poor outcome. The mutations seen in melanomas from other sites appear to be rarely present in these tumours.
Income inequality and health: the role of population size, inequality threshold, period effects and lag effects
Authors: Kondo Naoki , van Dam Rob M , Sembajwe Grace , Subramanian S V , Kawachi Ichiro , Yamagata Zentaro 
Published: October 2011

BackgroundIncome inequality has been associated with worse health outcomes in several but not all studies. The heterogeneity across studies may be explained by the variations in the size of area or population over which income inequality was evaluated. Moreover, the studies above a certain inequality threshold, conducted more recently, and incorporating a time lag may have stronger associations between income inequality and health. The authors investigated if the strength of the association between income inequality and health was altered by these factors.MethodsThe authors conducted a multivariate meta-regression analysis using nine multilevel cohort studies on income inequality and mortality and 14 multilevel cross-sectional studies on income inequality and self-rated health.ResultsAmong cross-sectional studies, studies evaluating country-level inequality (average population>24 million) were more likely to show a stronger association between income inequality and poor health compared with those evaluating income inequality within small average populations (<820 000). There were no significant differences in the effect size of inequality–health association relating to the differences in the population size within a country across which income inequality was evaluated in both cross-sectional and cohort studies. The authors found that the threshold effects, period effects and lag effects were independent of the population size.ConclusionsIncome inequality at the country level may have stronger adverse contextual effects on health than inequality in smaller areas, perhaps by best reflecting social stratification in a society. Furthermore, we found that threshold, period and lag effects were independent of area unit for evaluating inequality, which may have important policy implications.
Selective Antibody Response to Streptococcus gallolyticus Pilus Proteins in Colorectal Cancer Patients
Authors: Boleij Annemarie , Roelofs Rian , Danne Camille , Bellais Samuel , Dramsi Shaynoor , Kato Ikuko , Tjalsma Harold 
Published: October 2011

Abstract
Streptococcus gallolyticus subsp. gallolyticus (previously called Streptococcus bovis biotype I) infections have long been associated with colorectal cancer (CRC). This work aimed to investigate the CRC-associated humoral immune response to four pilus proteins of this bacterium by newly developed ELISAs. Pilus proteins are interesting diagnostic targets as they are the building blocks of pilin-like structures that mediate bacterial virulence and are readily exposed to the host immune system upon infection. The presence of serum antibodies against these pilus proteins was evaluated in Dutch and American populations. These analyses showed that an immune response to these antigens was specific for clinical S. gallolyticus subsp. gallolyticus infections, but that increased serum antibody titers to multiple pilus proteins in single individuals were rarely observed. However, a multiplex approach based on antibody titers against any of these four antigens resulted in assay sensitivities between 16% and 43% for the detection of early-stage CRC. Together these findings underscore the potential of a multi-antigen approach to complement diagnosis of S. gallolyticus subsp. gallolyticus–associated CRC. Cancer Prev Res; 5(2); 260–5. ©2011 AACR.