bluuebunny/crossref_metadata_2025_split huggingface dataset:
Herpes Simplex Virus 1 Ubiquitin Ligase ICP0 Interacts with PML Isoform I and Induces Its SUMO-Independent Degradation
Authors: Cuchet-Lourenço Delphine , Vanni Emilia , Glass Mandy , Orr Anne , Everett Roger D. 
Published: August 2012

ABSTRACT
Herpes simplex virus 1 (HSV-1) immediate-early protein ICP0 localizes to cellular structures known as promyelocytic leukemia protein (PML) nuclear bodies or ND10 and disrupts their integrity by inducing the degradation of PML. There are six PML isoforms with different C-terminal regions in ND10, of which PML isoform I (PML.I) is the most abundant. Depletion of all PML isoforms increases the plaque formation efficiency of ICP0-null mutant HSV-1, and reconstitution of expression of PML.I and PML.II partially reverses this improved replication. ICP0 also induces widespread degradation of SUMO-conjugated proteins during HSV-1 infection, and this activity is linked to its ability to counteract cellular intrinsic antiviral resistance. All PML isoforms are highly SUMO modified, and all such modified forms are sensitive to ICP0-mediated degradation. However, in contrast to the situation with the other isoforms, ICP0 also targets PML.I that is not modified by SUMO, and PML in general is degraded more rapidly than the bulk of other SUMO-modified proteins. We report here that ICP0 interacts with PML.I in both yeast two-hybrid and coimmunoprecipitation assays. This interaction is dependent on PML.I isoform-specific sequences and the N-terminal half of ICP0 and is required for SUMO-modification-independent degradation of PML.I by ICP0. Degradation of the other PML isoforms by ICP0 was less efficient in cells specifically depleted of PML.I. Therefore, ICP0 has two distinct mechanisms of targeting PML: one dependent on SUMO modification and the other via SUMO-independent interaction with PML.I. We conclude that the ICP0-PML.I interaction reflects a countermeasure to PML-related antiviral restriction.
Complete Genome Sequences of Novel Canine Noroviruses in Hong Kong
Authors: Tse Herman , Lau Susanna K. P. , Chan Wan-Mui , Choi Garnet K. Y. , Woo Patrick C. Y. , Yuen Kwok-Yung 
Published: August 2012

ABSTRACT
We report the complete genome sequences of two novel isolates of norovirus isolated from the fecal swab specimens of dogs in Hong Kong. The complete viral genome is approximately 7.6 kb in length and consists of 3 overlapping open reading frames encoding the ORF1 polyprotein, VP1, and VP2, respectively. Analysis of the VP1 sequence suggested that these noroviruses are divergent from known noroviruses and may represent a novel phylogenetic clade within the genus.
Genome Sequence of Herpes Simplex Virus 1 Strain McKrae
Authors: Macdonald Stuart J. , Mostafa Heba H. , Morrison Lynda A. , Davido David J. 
Published: August 2012

ABSTRACT
The herpes simplex virus 1 (HSV-1) strain McKrae is highly virulent compared to other wild-type strains of HSV-1. To help us better understand the genetic determinants that lead to differences in the pathogenicity of McKrae and other HSV-1 strains, we sequenced its genome. Comparing the sequence of McKrae's genome to that of strain 17 revealed that the genomes differ by at least 752 single nucleotide polymorphisms (SNPs) and 86 insertion/deletion events (indels). Although the majority of these polymorphisms reside in noncoding regions, 241 SNPs and 10 indels alter the protein-coding sequences of 58 open reading frames. Some of these variations are expected to contribute to the pathogenic phenotype of McKrae.
Complete Genome Sequencing of a Novel Newcastle Disease Virus Isolate Circulating in Layer Chickens in the Dominican Republic
Authors: Courtney Sean C. , Gomez Dejelia , Susta Leonardo , Hines Nichole , Pedersen Janice C. , Miller Patti J. , Afonso Claudio L. 
Published: August 2012

ABSTRACTNewcastle disease virus (NDV) was isolated from an outbreak in layer chickens in the Dominican Republic in 2008. Infections with this isolate led to a 100% apparent case fatality rate in birds. Complete genome sequencing revealed that the isolate does not belong to any of the previously described NDV genotypes. Similarly, large differences were observed in the amino acid sequence of the fusion and hemagglutinin-neuraminidase proteins in comparison with all known NDV genotypes, suggesting the existence of an unknown reservoir for NDV. The work presented here represents the first complete genome sequence of NDV in the Dominican Republic.
Vaccinia Virus Virion Membrane Biogenesis Protein A11 Associates with Viral Membranes in a Manner That Requires the Expression of Another Membrane Biogenesis Protein, A6
Authors: Wu Xiang , Meng Xiangzhi , Yan Bo , Rose Lloyd , Deng Junpeng , Xiang Yan 
Published: August 2012

ABSTRACT
A group of vaccinia virus (VACV) proteins, including A11, L2, and A6, are required for biogenesis of the primary envelope of VACV, specifically, for the acquisition of viral membrane precursors. However, the interconnection among these proteins is unknown and, with the exception of L2, the connection of these proteins with membranes is also unknown. In this study, prompted by the findings that A6 coprecipitated A11 and that the cellular distribution of A11 was dramatically altered by repression of A6 expression, we studied the localization of A11 in cells by using immunofluorescence and cell fractionation analysis. A11 was found to associate with membranes and colocalize with virion membrane proteins in viral replication factories during normal VACV replication. A11 partitioned almost equally between the detergent and aqueous phases upon Triton X-114 phase separation, demonstrating an intrinsic affinity with lipids. However, in the absence of infection or VACV late protein synthesis, A11 did not associate with cellular membranes. Furthermore, when A6 expression was repressed, A11 did not colocalize with any viral membrane proteins or associate with membranes. In contrast, when virion envelope formation was blocked at a later step by repression of A14 expression or by rifampin treatment, A11 colocalized with virion membrane proteins in the factories. Altogether, our data showed that A11 associates with viral membranes during VACV replication, and this association requires A6 expression. This study provides a physical connection between A11 and viral membranes and suggests that A6 regulates A11 membrane association.
HIV-1 Neutralizing Antibodies Display Dual Recognition of the Primary and Coreceptor Binding Sites and Preferential Binding to Fully Cleaved Envelope Glycoproteins
Authors: Li Yuxing , O'Dell Sijy , Wilson Richard , Wu Xueling , Schmidt Stephen D. , Hogerkorp Carl-Magnus , Louder Mark K. , Longo Nancy S. , Poulsen Christian , Guenaga Javier , Chakrabarti Bimal K. , Doria-Rose Nicole , Roederer Mario , Connors Mark , Mascola John R. , Wyatt Richard T. 
Published: August 2012

ABSTRACT
The gp120 CD4 binding site (CD4bs) and coreceptor binding site (CoRbs) are two functionally conserved elements of the HIV-1 envelope glycoproteins (Env). We previously defined the presence of CD4bs-neutralizing antibodies in the serum of an HIV-1-infected individual and subsequently isolated the CD4bs-specific monoclonal antibodies (MAbs) VRC01 and VRC03 from the memory B cell population. Since this donor's serum also appeared to contain neutralizing antibodies to the CoRbs, we employed a differential fluorescence-activated cell sorter (FACS)-based sorting strategy using an Env trimer possessing a CoRbs knockout mutation (I420R) to isolate specific B cells. The MAb VRC06 was recovered from these cells, and its genetic sequence allowed us to identify a clonal relative termed VRC06b, which was isolated from a prior cell sort using a resurfaced core gp120 probe and its cognate CD4bs knockout mutant. VRC06 and VRC06b neutralized 22% and 44% of viruses tested, respectively. Epitope mapping studies revealed that the two MAbs were sensitive to mutations in both the gp120 CoRbs and the CD4bs and could cross-block binding of both CD4bs and CoRbs MAbs to gp120. Fine mapping indicated contacts within the gp120 bridging sheet and the base of the third major variable region (V3), which are elements of the CoRbs. Cell surface binding assays demonstrated preferential recognition of fully cleaved Env trimers over uncleaved trimers. Thus, VRC06 and VRC06b are Env trimer precursor cleavage-sensitive neutralizing MAbs that bind to a region of gp120 that overlaps both the primary and the secondary HIV-1 receptor binding sites.
Structure, Function, and Evolution of the Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein
Authors: Carter Stephen D. , Surtees Rebecca , Walter Cheryl T. , Ariza Antonio , Bergeron Éric , Nichol Stuart T. , Hiscox Julian A. , Edwards Thomas A. , Barr John N. 
Published: August 2012

ABSTRACT

Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging tick-borne virus of the
Bunyaviridae
family that is responsible for a fatal human disease for which preventative or therapeutic measures do not exist. We solved the crystal structure of the CCHFV strain Baghdad-12 nucleocapsid protein (N), a potential therapeutic target, at a resolution of 2.1 Å. N comprises a large globular domain composed of both N- and C-terminal sequences, likely involved in RNA binding, and a protruding arm domain with a conserved DEVD caspase-3 cleavage site at its apex. Alignment of our structure with that of the recently reported N protein from strain YL04057 shows a close correspondence of all folds but significant transposition of the arm through a rotation of 180 degrees and a translation of 40 Å. These observations suggest a structural flexibility that may provide the basis for switching between alternative N protein conformations during important functions such as RNA binding and oligomerization. Our structure reveals surfaces likely involved in RNA binding and oligomerization, and functionally critical residues within these domains were identified using a minigenome system able to recapitulate CCHFV-specific RNA synthesis in cells. Caspase-3 cleaves the polypeptide chain at the exposed DEVD motif; however, the cleaved N protein remains an intact unit, likely due to the intimate association of N- and C-terminal fragments in the globular domain. Structural alignment with existing N proteins reveals that the closest CCHFV relative is not another bunyavirus but the arenavirus Lassa virus instead, suggesting that current segmented negative-strand RNA virus taxonomy may need revision.
Filamentous Influenza Virus Enters Cells via Macropinocytosis
Authors: Rossman Jeremy S. , Leser George P. , Lamb Robert A. 
Published: August 2012

ABSTRACT
Influenza virus is pleiomorphic, producing both spherical (100-nm-diameter) and filamentous (100-nm by 20-μm) virions. While the spherical virions are known to enter host cells through exploitation of clathrin-mediated endocytosis, the entry pathway for filamentous virions has not been determined, though the existence of an alternative, non-clathrin-, non-caveolin-mediated entry pathway for influenza virus has been known for many years. In this study, we confirm recent results showing that influenza virus utilizes macropinocytosis as an alternate entry pathway. Furthermore, we find that filamentous influenza viruses use macropinocytosis as the primary entry mechanism. Virions enter cells as intact filaments within macropinosomes and are trafficked to the acidic late-endosomal compartment. Low pH triggers a conformational change in the M2 ion channel protein, altering membrane curvature and leading to a fragmentation of the filamentous virions. This fragmentation may enable more-efficient fusion between the viral and endosomal membranes.
Clinical implications and validity of nursing assessments: a longitudinal measure of patient condition from analysis of the Electronic Medical Record
Authors: Rothman Michael J , Solinger Alan B , Rothman Steven I , Finlay G Duncan 
Published: August 2012

ObjectivesThis study investigates risk of mortality associated with nurses’ assessments of patients by physiological system. We hypothesise that nursing assessments of in-patients performed at entry correlate with in-hospital mortality, and those performed just before discharge correlate with postdischarge mortality.DesignCohort study of in-hospital and postdischarge mortality of patients over two 1-year periods.SettingAn 805-bed community hospital in Sarasota, Florida, USA.Subjects42 302 inpatients admitted for any reason, excluding obstetrics, paediatric and psychiatric patients.Outcome measuresAll-cause mortalities and mortality OR.ResultsPatients whose entry nursing assessments, other than pain, did not meet minimum standards had significantly higher in-hospital mortality than patients meeting minimums; and final nursing assessments before discharge had large OR for postdischarge mortality. In-hospital mortality OR were found to be: food, 7.0; neurological, 9.4; musculoskeletal, 6.9; safety, 5.6; psychosocial, 6.7; respiratory, 8.1; skin, 5.2; genitourinary, 3.0; gastrointestinal, 2.3; peripheral-vascular, 3.9; cardiac, 2.8; and pain, 1.1. CI at 95% are within ±20% of these values, with p<0.001 (except for pain). Similar results applied to postdischarge mortality. All results were comparable across the two 1-year periods, with 0.85 intraclass correlation coefficient.ConclusionsNursing assessments are strongly correlated with in-hospital and postdischarge mortality. No multivariate analysis has yet been performed, and will be the subject of a future study, thus there may be confounding factors. Nonetheless, we conclude that these assessments are clinically meaningful and valid. Nursing assessment data, which are currently unused, may allow physicians to improve patient care. The mortality OR and the dynamic nature of nursing assessments suggest that nursing assessments are sensitive indicators of a patient's condition. While these conclusions must remain qualified, pending future multivariate analyses, nursing assessment data ought to be incorporated in risk-related health research, and changes in record-keeping software are needed to make this information more accessible.
Impact of one or two visits strategy on hypertension burden estimation in HYDY, a population-based cross-sectional study: implications for healthcare resource allocation decision making
Authors: Modesti Pietro Amedeo , Rapi Stefano , Bamoshmoosh Mohamed , Baldereschi Marzia , Massetti Luciano , Padeletti Luigi , Gensini Gian Franco , Zhao Dong , Al-Hidabi Dawood , Al Goshae Husni 
Published: August 2012

ContextThe prevalence of hypertension in developing countries is coming closer to values found in developed countries. However, surveys usually rely on readings taken at a single visit, the option to implement the diagnosis on readings taken at multiple visits, being limited by costs.ObjectiveTo estimate more accurately the magnitude and extent of the resource that should be allocated to the prevention of hypertension.DesignPopulation-based cross-sectional survey with triplicate blood pressure (BP) readings taken on two separate home-visits.SettingRural and urban locations in three areas of Yemen (capital, inland and coast).ParticipantsA nationally representative sample of the Yemen population aged 15–69 years (5063 men and 5179 women), with an overall response rate of 92% in urban and 94% in rural locations.Main outcome measureHypertension diagnosed as systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg and/or self-reported use of antihypertensive drugs.ResultsHypertension prevalence (age-standardised to the WHO world population 2001) based on fulfilling the same criteria on both visits (11.3%; 95% Cl 10.7% to 11.9%), was 35% lower than estimation based on the first visit (17.3%; 16.5% to 18.0%). Advanced age, blood glucose ≥7 mmol/l or proteinuria ≥1+ at dipstick test at visit one were significant predictors of confirmation at visit 2. The 959 participants found to be hypertensive at visit 1 or at visit 2 only and thus excluded from the final diagnosis had a rate of proteinuria (5.0%; 3.8% to 6.5%) comparable to rates of the general population (6.1%; 5.6% to 6.6%), and of subjects normotensive at both visits (5.6%; 5.1% to 6.2%). Only 1.9% of Yemen population classified at high or very high cardiovascular (CV) risk at visit 1 moved to average, low or moderate CV risk categories after two visits.ConclusionsHypertension prevalence based on readings obtained after two visits is 35% lower than estimation based on the first visit, subjects were excluded from final diagnosis belonging to low CV risk classes.
Using care profiles as a catalyst for improving end of life commissioning, involvement and service delivery
Authors: Gandy Robert , Roe Brenda 
Published: August 2012

ObjectivesIn 2010, Liverpool Primary Care Trust successfully pioneered a care profiles approach to commissioning End of Life (EoL) services. They established service requirements for each stage of the EoL pathway, and set out skill mix, delivery, quality and outcomes. This feature sets out how the approach can also support local work relating to Advance Care Planning, palliative care funding tariffs and patient and public involvement.SituationLocal EoL services vary, reflecting geography, history, service models and resources. Few commissioners know in detail how all EoL services and resources systematically inter-relate, particularly those involving non-specialist services. Also, anecdotal evidence indicates that information provided by healthcare professionals to patients and carers is not necessarily consistent or complete.FinancesThe planned introduction of per patient tariffs for palliative care in 2015 means commissioners must be clear about what EoL services are and what are not covered by the tariffs, and how this might impact on service delivery and contracts.InformationA multi-disciplinary workshop established that by clarifying what services are commissioned locally, EoL care profiles can provide detailed information to ensure patients and carers receive comprehensive, consistent, quality information to support their Advanced Care Planning. They can address gaps in EoL information prescriptions and enable transparent information for patient and public involvement.ConclusionsEoL care profiles enable local services to be commissioned in detail, which is a catalyst and essential precursor for an inclusive and explicit approach to planning and resourcing services for individual patients and the population as a whole.
Is informal caregiving independently associated with poor health? A population-based study
Authors: Legg Lynn , Weir Chris J , Langhorne P , Smith L N , Stott D J 
Published: August 2012

BackgroundProviding informal care has been linked with poor health but has not previously been studied across a whole population. We aimed to study the association between informal care provision and self-reported poor health.MethodWe used data from the UK 2001 Census. The relationship between informal caregiving and poor health was modelled using logistic regression, adjusting for age, sex, marital status, ethnicity, economic activity and educational attainment.ResultsWe included 44 465 833 individuals free from permanent sickness or disability. 5 451 902 (12.3%) participants reported providing informal care to another person. There was an association between provision of informal caregiving and self-reported poor health; OR 1.100, 95% CI 1.096 to 1.103. This association remained after adjustment for age, sex, ethnic group, marital status, economic activity and educational attainment. The association also increased with the amount of care provided (hours per week).ConclusionsAround one in eight of the UK population reports that he or she is an informal caregiver. This activity is associated with poor health, particularly in those providing over 20 h care per week.
Unprotected fellatio between female sex workers and their clients in Sydney, Australia
Authors: Read Phillip J , Wand Handan , Guy Rebecca , Donovan Basil , McNulty Anna M 
Published: August 2012

ObjectivesTo assess the frequency and predictors of inconsistent condom use for fellatio at work by female sex workers (FSW) in Sydney and the prevalence of pharyngeal gonorrhoea and other sexually transmitted infections in these women.MethodsCross-sectional study including all FSW attending the Sydney Sexual Health Centre for sexually transmitted infection screening between May 2009 and January 2011 and reporting fellatio at work. Univariate and multivariate regression was used to identify predictors of inconsistent condom use for fellatio.ResultsOf 1540 FSW who offered fellatio at work, 372 (25%) reported inconsistent condom use for this fellatio. In multivariate analysis, speaking Mandarin or Cantonese rather than English (adjusted OR (AOR) 2.03, 95% CI 1.44 to 2.86), reporting inconsistent condom use for vaginal sex at work (AOR 10.82, 95% CI 6.13 to 19.09), reporting no vaginal sex at work (AOR 7.48, 95% CI 2.42 to 23.12) and being a new client to the clinic (AOR 2.10, 95% CI 1.56 to 2.83) were associated with inconsistent condom use for fellatio. Thai-speaking women were less likely to report unprotected fellatio (AOR 0.36, 95% CI 0.23 to 0.57). 17 women were diagnosed with pharyngeal gonorrhoea (AOR 1.1%, 95% CI 0.6% to 1.7%).ConclusionsCondom use for fellatio by Sydney FSW varies by work location and language spoken. Health promotion targeting these at-risk women is warranted. Women working in brothels masquerading as massage parlours were particularly likely to report inconsistent condom use for fellatio. Local government reluctance to approve brothels may be contributing to this problem.
Anaemia in the sow: a cohort study to assess factors with an impact on haemoglobin concentration, and the influence of haemoglobin concentration on the reproductive performance
Authors: Normand V. , Perrin H. , Auvigne V. , Robert N. , Laval A. 
Published: August 2012

The aim of this study was to conduct a descriptive study of haemoglobin concentration found on high‐prolificacy sows, to study the relationship between the concentration of haemoglobin and body reserves, and to determine whether anaemia is a risk factor for reproductive performance. A cohort of 308 sows from seven farms was followed from the last third of gestation to the confirmation of the following gestation. Haemoglobin concentration was assessed at four stages of the reproductive cycle: seven and four weeks before farrowing, a few days and three weeks after farrowing. Backfat thickness (BFT) was measured at parturition. The results were analysed using linear mixed‐effect models. The mean haemoglobin concentration was 108.4 g/l. The mean modellised haemoglobin concentration of parity 1 sows with a BFT of 16 mm, sampled seven weeks before farrowing, was 118 g/l. Haemoglobin concentration of sows of parity 6 or higher was 8.0 g/l lower than those of parity 1 sows (95% confidence interval −11.0 to −5.1). Haemoglobin concentration is lower in sows with a lower BFT, whatever parity rank. There is no evidence of a relation between haemoglobin concentration and the number of total born, stillborn or number of piglets alive at three weeks and the next breeding performance.
Synthesis of heteroleptic pyrrolide/bipyridyl complexes of ruthenium(II)
Authors: Lundrigan Travis , Jackson Carla L.M. , Uddin Md. Imam , Tucker Lloyd A. , Ali Adeeb Al-Sheikh , Linden Anthony , Cameron T. Stanley , Thompson Alison 
Published: August 2012

The synthesis and characterization of the first heteroleptic pyrrolide/2,2′-bipyridyl complexes of ruthenium(II) are reported. Pyrroles substituted at the 2-position with X = O functionality react with Ru(bipy)2Cl2·2H2O to form complexes in which the pyrrolide ligands chelate to Ru(II). The library of pyrroles includes 2-formyl, 2-keto, 2-carboxylato, 2-sulfinyl, and 2-sulfonyl derivatives.