bluuebunny/crossref_metadata_2025 huggingface dataset:
Registered nurses' perceptions of conditions for patient education – focusing on aspects of competence
Authors: Bergh Anne‐Louise , Persson Eva , Karlsson Jan , Friberg Febe
Published: August 2013

Background

It is important to clarify nurses' perceptions of conditions for patient education in daily work as research findings are ambiguous. There is a gap between societal regulations on nurses' competence in accomplishment/achievement of patient education and research findings.

Aim

The aim was to describe nurses' perceptions of conditions for patient education, focusing on aspects of competence. The aim was also to describe differences in conditions for nurses working in primary, municipal and hospital care.

Methods

The study is a cross‐sectional survey and is part of a project about nurses' patient‐education. A randomized selection of nurses (842) received a questionnaire comprising 47 items concerning factual experience and attitudes to patient education and 13 background items. Questionnaires were returned by 83% of participants. Descriptive statistics, non‐parametric tests and content analysis for open‐ended items were used.

Results

Nurses' perceptions of conditions for patient education differ between health‐care settings. Primary care nurses are at an advantage in following research in patient education, perception of their own competence (prioritizing and knowing their mandate in patient teaching), pedagogical education and post graduate specializations.

Conclusions

Nurses' patient education must be more visualized and appropriate conditions created at each workplace. In this change process, managers' support is considered vital.
Three‐dimensional organization of local excitatory and inhibitory inputs to neurons in laminae III–IV of the spinal dorsal horn
Authors: Kato Go , Kosugi Masafumi , Mizuno Masaharu , Strassman Andrew M.
Published: August 2013

Key points

Axons of sensory neurons that detect painful and non‐painful stimulation of body tissues project centrally to the dorsal horn of the spinal cord, where they are partially segregated in the superficial and deep laminae, respectively.

Interneuronal connections between superficial and deep laminae could potentially modulate sensory transmission and contribute to alterations that occur under conditions of pain hypersensitivity.

This study used a localized stimulation technique (laser scanning photostimulation) for high‐resolution mapping of local interneuronal synaptic connections to laminae III–IV neurons, combined with intracellular staining for morphological analysis, in an in vitro‘slice’ preparation of the rat lumbar spinal cord.

Synaptic input from superficial laminae (I–II) was received by laminae III–IV neurons with long dorsal dendrites, supporting the idea that interlaminar connectivity is mediated via translaminar dendritic extensions and, more generally, that local connectivity is governed by rules that are specific to the laminar position and morphology of the postsynaptic neuron.

Abstract  Laser scanning photostimulation was used to map the distribution of the synaptic input zones (sites that give local synaptic inputs) for dorsal horn laminae III–IV neurons, in parasagittal and transverse slices of the rat lumbar spinal cord, and examine how these inputs differed for neurons of different morphologies. All neurons received local excitatory and inhibitory synaptic inputs from within laminae III–IV, while a subset of neurons also received excitatory input from the superficial laminae, especially lamina IIi, as well as the II/III border region. Two anatomical properties were found to be predictive of the dorsoventral position of a neuron's input zone relative to its soma: (1) both excitatory and inhibitory input zones were more dorsal for neurons with longer dorsal dendrites, and (2) excitatory, but not inhibitory, input zones were more dorsal (relative to the soma) for more ventral neurons, with the transition between the dorsal input zones of laminae III–IV neurons and the ventral input zones of lamina II neurons occurring at the II/III border. The observed morphophysiological correlations support the idea that interlaminar connectivity is mediated via translaminar dendritic extensions and that, more generally, local connectivity within the dorsal horn is governed by rules relating the position of a neuron's soma and dendrites to the position of the local presynaptic neurons from which it receives inputs, which are specific to the axis and direction (dorsal vs. ventral), whether the input is excitatory or inhibitory, and the laminar position of the postsynaptic neuron.
Discrepancies in the nature of nitrogen incorporation in dilute-nitride GaSbN and GaAsN films
Authors: Sarney Wendy L. , Svensson Stefan P.
Published: August 2013

The authors studied the incorporation of dilute concentrations of nitrogen into GaSb and GaAs. There is a dissimilar interaction of N-Sb compared to N-As for films grown in the same manner, as indicated by discrepancies in x-ray diffraction and chemical analysis, and consistent with measured changes in the bandgap. The N in GaSb1−xNx resides in a quantifiable, “dark” phase correlating with the larger negative impact on the GaSb1−xNx optical properties relative to GaAs1−xNx. The authors hypothesize that the missing N resides in a phase that is optically inactive or have a much wider bandgap than the matrix material.
Crystal Structure of MraY, an Essential Membrane Enzyme for Bacterial Cell Wall Synthesis
Authors: Chung Ben C. , Zhao Jinshi , Gillespie Robert A. , Kwon Do-Yeon , Guan Ziqiang , Hong Jiyong , Zhou Pei , Lee Seok-Yong
Published: August 2013

Moving Bricks with MraY

Peptidoglycan, the building brick of bacterial cell walls, is synthesized in the cytoplasm and must be transported across the cell membrane. To achieve this, it is attached to a carrier lipid by the integral membrane protein MraY. MraY is targeted by natural antibacterials and is a promising antibiotic target.

Chung
et al.

(p.
1012
) report the crystal structure of MraY at 3.3 Å resolution. The structure, together with mutational mapping, outlines the location of the active site and provides interesting hints for how the enzyme binds the substrate and catalyzes attachment to the carrier lipid.
Minimizing Caribbean Tsunami Risk
Authors: von Hillebrandt-Andrade Christa
Published: August 2013

Efforts to understand and respond to tsunami risks in the Caribbean are beginning to bear fruit.
Nuclear Wave1 Is Required for Reprogramming Transcription in Oocytes and for Normal Development
Authors: Miyamoto Kei , Teperek Marta , Yusa Kosuke , Allen George E , Bradshaw Charles R , Gurdon J. B.
Published: August 2013

Egg WAVE1

Eggs not only activate sperm nuclei for normal development but also reprogram transplanted somatic nuclei. In addition to its well-established cytoplasmic role in actin organization,

Miyamoto
et al.

(p.
1002
) discovered that the Wiskott-Aldrich syndrome protein family member 1 in oocytes cooperates with transcriptional machineries in the nucleus to activate previously silenced genes.
Dissecting X-ray–Emitting Gas Around the Center of Our Galaxy
Authors: Wang Q. D. , Nowak M. A. , Markoff S. B. , Baganoff F. K. , Nayakshin S. , Yuan F. , Cuadra J. , Davis J. , Dexter J. , Fabian A. C. , Grosso N. , Haggard D. , Houck J. , Ji L. , Li Z. , Neilsen J. , Porquet D. , Ripple F. , Shcherbakov R. V.
Published: August 2013

The Galaxy Center in X-rays

At the center of our Galaxy there is a black hole 4-million-fold more massive than the Sun.

Wang
et al.

(p.
981
; see the Perspective by

Schnittman

) report x-ray data on the accretion flow around this supermassive black hole, revealing how it interacts with its surroundings. The data rule out the possibility that the quiescent (that is, flare-free) x-rays observed are produced by coronal emission from a population of stars at the center of the Galaxy and also rule out the possibility that there is a pure radiatively inefficient accretion flow with no outflows.
Confronting the Sorry State of U.S. Health
Authors: Bayer Ronald , Fairchild Amy L. , Hopper Kim , Nathanson Constance A.
Published: August 2013

President Obama should convene a National Commission on the Health of Americans to address the social causes that have put the U.S.A. last among comparable nations.
The Curious Behavior of the Milky Way's Central Black Hole
Authors: Schnittman Jeremy D.
Published: August 2013

X-ray observations of the supermassive black hole at the galactic center help explain the unusually inefficient accretion of surrounding gas.

[Also see Report by

Wang
et al.

]
Accelerating Ocean Exploration
Authors: McNutt Marcia
Published: August 2013

Last month, a distinguished group of ocean researchers and explorers convened in Long Beach, California, at the Aquarium of the Pacific to assess progress and future prospects in ocean exploration. Thirteen years ago, U.S. President Clinton challenged a similar group to provide a blueprint for ocean exploration and discovery. Since then, the fundamental rationale has not changed: to collect high-quality data on the physics, chemistry, biology, and geology of the oceans that can be used to answer known questions as well as those we do not yet know enough to pose, to develop new instruments and systems to explore the ocean in new dimensions, and to engage a new generation of youth in science and technology. Recently, however, exploration has taken on a more urgent imperative: to record the substantial changes occurring in largely undocumented regions of the ocean. With half of the ocean more than 10 kilometers from the nearest depth sounding, ecosystem function in the deep sea still a mystery, and no first-order baseline for many globally important ocean processes, the current pace of exploration is woefully inadequate to address this daunting task, especially as the planet responds to changes in climate. To meet this challenge, future ocean exploration must depart dramatically from the classical ship-based expeditions of the past devoted to mapping and sampling.
The Poor's Poor Mental Power
Authors: Vohs Kathleen D.
Published: August 2013

Poverty's mental toll might explain its connection to unhealthy impulsive behaviors.

[Also see Research Article by

Mani
et al.

]
Targeting Noncoding RNAs in Disease: Challenges and Opportunities
Authors: Corey David R. , Dimmeler Stefanie , Kornfeld Jan-Wilhelm
Published: August 2013

Noncoding RNAs make up the majority of transcribed RNA and have a wide range of functions in cellular and developmental processes. Consequently, they are also implicated in the development and pathophysiology of many diseases and represent potential targets for therapeutic intervention. microRNAs are one class of noncoding RNA that has been intensely studied. Effective inhibition (or silencing) of microRNAs in vivo has enabled scientists to make groundbreaking discoveries about the contribution of these short regulating RNAs to some of the major human diseases, such as cancer, heart disease, and diabetes. Long noncoding RNAs are less well studied, but have recently emerged as another novel class of therapeutic targets in a variety of diseases. Both long and short noncoding RNAs represent new avenues of investigation for drug discovery with several advantages over traditional protein-based targets; however, they come with their own unique set of challenges.
Taking the Life Out of Titan
Authors: Kerr Richard A.
Published: August 2013

Is Saturn's big, haze-shrouded moon Titan dead or alive?
Dynamics of Defective Hepatitis C Virus Clones in Reinfected Liver Grafts in Liver Transplant Recipients: Ultradeep Sequencing Analysis
Authors: Ohtsuru Shigeru , Ueda Yoshihide , Marusawa Hiroyuki , Inuzuka Tadashi , Nishijima Norihiro , Nasu Akihiro , Shimizu Kazuharu , Koike Kaoru , Uemoto Shinji , Chiba Tsutomu
Published: August 2013

Hepatitis C virus (HCV) reinfects liver allografts in transplant recipients by replicating immediately after transplantation, causing a rapid increase in blood serum HCV RNA levels. We evaluated dynamic changes in the viral genetic complexity after HCV reinfection of the graft liver; we also identified the characteristics of replicating HCV clones using a massively parallel ultradeep sequencing technique to determine the full-genome HCV sequences in the liver and serum specimens of five transplant recipients with genotype 1b HCV infection before and after liver transplantation. The recipients showed extremely high genetic heterogeneity before transplantation, and the HCV population makeup was not significantly different between the liver and blood serum specimens of the individuals. Viral quasispecies complexity in serum was significantly lower after liver transplantation than before it, suggesting that certain HCV clones selectively proliferated after transplantation. Defective HCV clones lacking the structural region of the HCV genome did not increase in number, and full-genome HCV clones selectively increased in number immediately after liver transplantation. A re-increase in the same defective clone existing before transplantation was detected 22 months after transplantation in one patient. Ultradeep sequencing technology revealed that the genetic heterogeneity of HCV was reduced after liver transplantation. Dynamic changes in defective HCV clones after liver transplantation indicate that these clones have important roles in the HCV life cycle.
Splitting of a Prevalent Mycobacterium bovis Spoligotype by Variable-Number Tandem-Repeat Typing Reveals High Heterogeneity in an Evolving Clonal Group
Authors: Rodriguez-Campos Sabrina , Navarro Yurena , Romero Beatriz , de Juan Lucía , Bezos Javier , Mateos Ana , Golby Paul , Smith Noel H. , Hewinson Glyn R. , Domínguez Lucas , García-de-Viedma Darío , Aranaz Alicia
Published: August 2013

Mycobacterium bovis
populations in countries with persistent bovine tuberculosis usually show a prevalent spoligotype with a wide geographical distribution. This study applied mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) typing to a random panel of 115
M. bovis
isolates that are representative of the most frequent spoligotype in the Iberian Peninsula, SB0121. VNTR typing targeted nine loci: ETR-A (alias VNTR2165), ETR-B (VNTR2461), ETR-D (MIRU4, VNTR580), ETR-E (MIRU31, VNTR3192), MIRU26 (VNTR2996), QUB11a (VNTR2163a), QUB11b (VNTR2163b), QUB26 (VNTR4052), and QUB3232 (VNTR3232). We found a high degree of diversity among the studied isolates (discriminatory index [D] = 0.9856), which were split into 65 different MIRU-VNTR types. An alternative short-format MIRU-VNTR typing targeting only the four loci with the highest variability values was found to offer an equivalent discriminatory index. Minimum spanning trees using the MIRU-VNTR data showed the hypothetical evolution of an apparent clonal group. MIRU-VNTR analysis was also applied to the isolates of 176 animals from 15 farms infected by
M. bovis
SB0121; in 10 farms, the analysis revealed the coexistence of two to five different MIRU types differing in one to six loci, which highlights the frequency of undetected heterogeneity.
The Aptima HPV Assay Fulfills the Cross-Sectional Clinical and Reproducibility Criteria of International Guidelines for Human Papillomavirus Test Requirements for Cervical Screening
Authors: Heideman D. A. M. , Hesselink A. T. , van Kemenade F. J. , Iftner T. , Berkhof J. , Topal F. , Agard D. , Meijer C. J. L. M. , Snijders P. J. F.
Published: August 2013

The Aptima HPV assay (Hologic Gen-Probe, San Diego, CA) is an FDA-approved assay for detecting human papillomavirus (HPV) E6/E7 mRNA from 14 high-risk HPV types. This study evaluated the clinical performance of the Aptima HPV assay for cervical intraepithelial neoplasia of grade 2 or worse (CIN2+), relative to the high-risk HPV GP5+/GP6+ PCR, in a cross-sectional clinical equivalence analysis using the noninferiority score test with cervical samples from population-based screening, i.e., 69 cervical scraping samples from women with CIN2+ and 843 from women without evidence of CIN2+. In addition, intralaboratory reproducibility over time and interlaboratory agreement of the Aptima HPV assay results were assessed with another set of 548 cervical samples. The Aptima HPV assay showed a clinical sensitivity for CIN2+ of 94.2% (95% confidence interval [CI], 85.5 to 97.8%) and a clinical specificity for CIN2+ of 94.5% (95% CI, 92.8 to 95.9%); by comparison, these figures were 97.1% (95% CI, 89.1 to 99.3%) (67/69 samples) and 93.6% (95% CI, 91.7 to 95.0%) (785/839 samples), respectively, for GP5+/GP6+ PCR. The clinical sensitivity and specificity of the Aptima HPV assay were noninferior to those of GP5+/GP6+ PCR (
P
= 0.039 and 0.00016, respectively). In addition, high reproducibility of the Aptima HPV assay, as reflected by the intralaboratory reproducibility over time of 96.0% (95% CI, 94.4 to 97.3%) (526/548 samples; kappa = 0.89) and interlaboratory agreement of 96.7% (95% CI, 95.4 to 98.1%) (531/548 samples; kappa = 0.91), was found. Altogether, these data show that the Aptima HPV assay meets the cross-sectional clinical and reproducibility criteria of the international guidelines for HPV test requirements for cervical screening. Longitudinal data are needed to ensure that the long-term negative predictive value of this mRNA assay is similar to those of validated HPV DNA tests.
Novel Approach for Differentiating Shigella Species and Escherichia coli by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Authors: Khot Prasanna D. , Fisher Mark A.
Published: August 2013

Shigellaspecies are so closely related toEscherichia colithat routine matrix-assisted laser desorption/ionization–time of flight mass spectrometry (MALDI-TOF MS) cannot reliably differentiate them. Biochemical and serological methods are typically used to distinguish these species; however, “inactive” isolates ofE. coliare biochemically very similar toShigellaspecies and thus pose a greater diagnostic challenge. We used ClinProTools (Bruker Daltonics) software to discover MALDI-TOF MS biomarker peaks and to generate classification models based on the genetic algorithm to differentiate betweenShigellaspecies andE. coli.Sixty-sixShigellaspp. and 72E. coliisolates were used to generate and test classification models, and the optimal models contained 15 biomarker peaks for genus-level classification and 12 peaks for species-level classification. We were able to identify 90% ofE. coliandShigellaclinical isolates correctly to the species level. Only 3% of tested isolates were misidentified. This novel MALDI-TOF MS approach allows laboratories to streamline the identification ofE. coliandShigellaspecies.
Comparison of Nucleic Acid Amplification Assays with BD Affirm VPIII for Diagnosis of Vaginitis in Symptomatic Women
Authors: Cartwright Charles P. , Lembke Bryndon D. , Ramachandran Kalpana , Body Barbara A. , Nye Melinda B. , Rivers Charles A. , Schwebke Jane R.
Published: August 2013

A commercially available, nonamplified, nucleic acid probe-based test system (BD Affirm VPIII) was compared with nucleic acid amplification (NAA)-based assays for determining the etiology of vaginitis in a cohort of 323 symptomatic women. First, a semiquantitative, multiplexed PCR assay (BV-PCR) and the Affirm VPIII
Gardnerella
vaginalis
test were compared with a unified bacterial-vaginosis (BV) reference standard incorporating both Nugent Gram stain scores and Amsel clinical criteria. In the evaluable population of 305 patients, BV-PCR was 96.9% (191/197) sensitive and 92.6% specific (100/108) for BV, while Affirm VPIII was 90.1% sensitive (179/197) and 67.6% specific (73/108). Second, a multiplexed PCR assay detecting
Candida albicans
and
Candida glabrata
(CAN-PCR) was compared with the Affirm VPIII
Candida
test using a reference standard for vulvovaginal candidiasis (VVC) of yeast culture plus exclusion of alternate vaginitis etiologies. In the population evaluated (
n
= 102), CAN-PCR was 97.7% sensitive (42/43) and 93.2% specific (55/59) and Affirm VP III was 58.1% sensitive (25/43) and 100% specific (59/59) for VVC. Finally, the results of a commercial NAA test (GenProbe Aptima
Trichomonas vaginalis
assay; ATV) for
T. vaginalis
were compared with the Affirm VPIII
Trichomonas vaginalis
test. In the absence of an independent reference standard for trichomonal vaginitis (TV), a positive result in either assay was deemed to represent true infection. In the evaluable cohort of 388 patients, the sensitivity of ATV was 98.1% (53/54) versus 46.3% (25/54) for Affirm VPIII. The diagnostic accuracy of the combined NAA-based test construct was approximately 20 to 25% higher than that of the Affirm VPIII when modeled in populations with various prevalences of infectious vaginitis.
Autocatalytic Cleavage within Classical Swine Fever Virus NS3 Leads to a Functional Separation of Protease and Helicase
Authors: Lamp Benjamin , Riedel Christiane , Wentz Eveline , Tortorici Maria-Alejandra , Rümenapf Till
Published: August 2013

Classical swine fever virus (CSFV) is a positive-stranded RNA virus belonging to the genus
Pestivirus
within the
Flaviviridae
family. Pivotal for processing of a large portion of the viral polyprotein is a serine protease activity within nonstructural protein 3 (NS3) that also harbors helicase and NTPase activities essential for RNA replication. In CSFV-infected cells, NS3 appears as two forms, a fully processed NS3 of 80 kDa and the precursor molecule NS2-3 of 120 kDa. Here we report the identification and mapping of additional autocatalytic intramolecular cleavages. One cleavable peptide bond occurs between Leu
1781
and Met
1782
, giving rise to a helicase subunit of 55 kDa and, depending on the substrate, a NS2-3 fragment of 78 kDa (NS2-3p) or a NS3 protease subunit of 26 kDa (NS3p). In
trans
-cleavage assays using NS4-5 as a substrate, NS3p acts as a fully functional protease that is able to process the polyprotein. NS3p comprises the minimal essential protease, as deletion of Leu
1781
results in inactivation. A second intramolecular cleavage was mapped to the Leu
1748
/Lys
1749
peptide bond that yields a proteolytically inactive NS3 fragment. Deletion of either of the cleavage site residues resulted in a loss of RNA infectivity, indicating the functional importance of amino acid identity at the respective positions. Our data suggest that internal cleavage within the NS3 moiety is a common process that further extends the functional repertoires of the multifunctional NS2-3 or NS3 and represents another level of the complex polyprotein processing of
Flaviviridae
.
TLR3- and MyD88-Dependent Signaling Differentially Influences the Development of West Nile Virus-Specific B Cell Responses in Mice following Immunization with RepliVAX WN, a Single-Cycle Flavivirus Vaccine Candidate
Authors: Xia Jingya , Winkelmann Evandro R. , Gorder Summer R. , Mason Peter W. , Milligan Gregg N.
Published: August 2013

Recognition of conserved pathogen-associated molecular patterns (PAMPs) by host pattern recognition receptors (PRRs) results in the activation of innate signaling pathways that drive the innate immune response and ultimately shape the adaptive immune response. RepliVAX WN, a single-cycle flavivirus (SCFV) vaccine candidate derived from West Nile virus (WNV), is intrinsically adjuvanted with multiple PAMPs and induces a vigorous anti-WNV humoral response. However, the innate mechanisms that link pattern recognition and development of vigorous antigen-specific B cell responses are not completely understood. Moreover, the roles of individual PRR signaling pathways in shaping the B cell response to this live attenuated SCFV vaccine have not been established. We examined and compared the role of TLR3- and MyD88-dependent signaling in the development of anti-WNV-specific antibody-secreting cell responses and memory B cell responses induced by RepliVAX WN. We found that MyD88 deficiency significantly diminished B cell responses by impairing B cell activation, development of germinal centers (GC), and the generation of long-lived plasma cells (LLPCs) and memory B cells (MBCs). In contrast, TLR3 deficiency had more effect on maintenance of GCs and development of LLPCs, whereas differentiation of MBCs was unaffected. Our data suggest that both TLR3- and MyD88-dependent signaling are involved in the intrinsic adjuvanting of RepliVAX WN and differentially contribute to the development of vigorous WNV-specific antibody and B cell memory responses following immunization with this novel SCFV vaccine.
Mutations in DNA Binding and Transactivation Domains Affect the Dynamics of Parvovirus NS1 Protein
Authors: Niskanen Einari A. , Kalliolinna Olli , Ihalainen Teemu O. , Häkkinen Milla , Vihinen-Ranta Maija
Published: August 2013

The multifunctional replication protein of autonomous parvoviruses, NS1, is vital for viral genome replication and for the control of viral protein production. Two DNA-interacting domains of NS1, the N-terminal and helicase domains, are necessary for these functions. In addition, the N and C termini of NS1 are required for activation of viral promoter P38. By comparison with the structural and biochemical data from other parvoviruses, we identified potential DNA-interacting amino acid residues from canine parvovirus NS1. The role of the identified amino acids in NS1 binding dynamics was studied by mutagenesis, fluorescence recovery after photobleaching, and computer simulations. Mutations in the predicted DNA-interacting amino acids of the N-terminal and helicase domains increased the intranuclear binding dynamics of NS1 dramatically. A substantial increase in binding dynamics was also observed for NS1 mutants that targeted the metal ion coordination site in the N terminus. Interestingly, contrary to other mutants, deletion of the C terminus resulted in slower binding dynamics of NS1. P38 transactivation was severely reduced in both N-terminal DNA recognition and in C-terminal deletion mutants. These data suggest that the intranuclear dynamics of NS1 are largely characterized by its sequence-specific and -nonspecific binding to double-stranded DNA. Moreover, binding of NS1 is equally dependent on the N-terminal domain and conserved β-loop of the helicase domain.
Recombination-Dependent Oligomerization of Human Papillomavirus Genomes upon Transient DNA Replication
Authors: Orav Marit , Henno Liisi , Isok-Paas Helen , Geimanen Jelizaveta , Ustav Mart , Ustav Ene
Published: August 2013

We describe the extensive and progressive oligomerization of human papillomavirus (HPV) genomes after transfection into the U2OS cell line. The HPV genomic oligomers are extrachromosomal concatemeric molecules containing the viral genome in a head-to-tail orientation. The process of oligomerization does not depend on the topology of the input DNA, and it does not require any other viral factors besides replication proteins E1 and E2. We provide evidence that oligomerization of the HPV18 and HPV11 genomes involves homologous recombination. We also demonstrate oligomerization of the HPV18 and HPV11 genomes in SiHa, HeLa, and C-33 A cell lines and provide examples of oligomeric HPV genomes in clinical samples obtained from HPV-infected patients.
Inhibition of CUL4A Neddylation Causes a Reversible Block to SAMHD1-Mediated Restriction of HIV-1
Authors: Hofmann Henning , Norton Thomas D. , Schultz Megan L. , Polsky Sylvie B. , Sunseri Nicole , Landau Nathaniel R.
Published: August 2013

The deoxynucleoside triphosphohydrolase SAMHD1 restricts retroviral replication in myeloid cells. Human immunodeficiency virus type 2 (HIV-2) and a simian immunodeficiency virus from rhesus macaques (SIVmac) encode Vpx, a virion-packaged accessory protein that counteracts SAMHD1 by inducing its degradation. SAMHD1 is thought to work by depleting the pool of intracellular deoxynucleoside triphosphates but has also been reported to have exonuclease activity that could allow it to degrade the viral genomic RNA or viral reverse-transcribed DNA. To induce the degradation of SAMHD1, Vpx co-opts the cullin4a-based E3 ubiquitin ligase, CRL4. E3 ubiquitin ligases are regulated by the covalent attachment of the ubiquitin-like protein Nedd8 to the cullin subunit. Neddylation can be prevented by MLN4924, a drug that inhibits the nedd8-activating enzyme. We report that MLN4924 inhibits the neddylation of CRL4, blocking Vpx-induced degradation of SAMHD1 and maintaining the restriction. Removal of the drug several hours postinfection released the block. Similarly, Vpx-containing virus-like particles and deoxynucleosides added to the cells more than 24 h postinfection released the SAMHD1-mediated block. Taken together, these findings support deoxynucleoside triphosphate pool depletion as the primary mechanism of SAMHD1 restriction and argue against a nucleolytic mechanism, which would not be reversible.
EBNA3C-Mediated Regulation of Aurora Kinase B Contributes to Epstein-Barr Virus-Induced B-Cell Proliferation through Modulation of the Activities of the Retinoblastoma Protein and Apoptotic Caspases
Authors: Jha Hem Chandra , Lu Jie , Saha Abhik , Cai Qiliang , Banerjee Shuvomoy , Prasad Mahadesh A. J. , Robertson Erle S.
Published: August 2013

Epstein-Barr virus (EBV) is an oncogenic gammaherpesvirus that is implicated in several human malignancies, including Burkitt's lymphoma (BL), posttransplant lymphoproliferative disease (PTLD), nasopharyngeal carcinoma (NPC), and AIDS-associated lymphomas. Epstein-Barr nuclear antigen 3C (EBNA3C), one of the essential EBV latent antigens, can induce mammalian cell cycle progression through its interaction with cell cycle regulators. Aurora kinase B (AK-B) is important for cell division, and deregulation of AK-B is associated with aneuploidy, incomplete mitotic exit, and cell death. Our present study shows that EBNA3C contributes to upregulation of AK-B transcript levels by enhancing the activity of its promoter. Further, EBNA3C also increased the stability of the AK-B protein, and the presence of EBNA3C leads to reduced ubiquitination of AK-B. Importantly, EBNA3C in association with wild-type AK-B but not with its kinase-dead mutant led to enhanced cell proliferation, and AK-B knockdown can induce nuclear blebbing and cell death. This phenomenon was rescued in the presence of EBNA3C. Knockdown of AK-B resulted in activation of caspase 3 and caspase 9, along with poly(ADP-ribose) polymerase 1 (PARP1) cleavage, which is known to be an important contributor to apoptotic signaling. Importantly, EBNA3C failed to stabilize the kinase-dead mutant of AK-B compared to wild-type AK-B, which suggests a role for the kinase domain in AK-B stabilization and downstream phosphorylation of the cell cycle regulator retinoblastoma protein (Rb). This study demonstrates the functional relevance of AK-B kinase activity in EBNA3C-regulated B-cell proliferation and apoptosis.
Redox and Light Control the Heme-Sensing Activity of AppA
Authors: Yin Liang , Dragnea Vladimira , Feldman George , Hammad Loubna A. , Karty Jonathan A. , Dann Charles E. , Bauer Carl E.
Published: August 2013

The DNA binding activity of the photosystem-specific repressor PpsR is known to be repressed by the antirepressor AppA. AppA contains a blue-light-absorbing BLUF domain and a heme-binding SCHIC domain that controls the interaction of AppA with PpsR in response to light and heme availability. In this study, we have solved the structure of the SCHIC domain and identified the histidine residue that is critical for heme binding. We also demonstrate that dark-adapted AppA binds heme better than light-excited AppA does and that heme bound to the SCHIC domain significantly reduces the length of the BLUF photocycle. We further show that heme binding to the SCHIC domain is affected by the redox state of a disulfide bridge located in the Cys-rich carboxyl-terminal region. These results demonstrate that light, redox, and heme are integrated inputs that control AppA’s ability to disrupt the DNA binding activity of PpsR.

IMPORTANCEPhotosynthetic bacteria must coordinate synthesis of the tetrapyrroles cobalamin, heme, and bacteriochlorophyll, as overproduction of the latter two is toxic to cells. A key regulator controlling tetrapyrrole biosynthesis is PpsR, and the activity of PpsR is controlled by the heme-binding and light-regulated antirepressor AppA. We show that AppA binds heme only under dark conditions and that heme binding significantly affects the length of the AppA photocycle. Since AppA interacts with PpsR only in the dark, bound heme thus stimulates the antirepressor activity of PpsR. This causes the redirection of tetrapyrrole biosynthesis away from heme into the bacteriochlorophyll branch.
Role of Protein A in the Evasion of Host Adaptive Immune Responses by Staphylococcus aureus
Authors: Falugi Fabiana , Kim Hwan Keun , Missiakas Dominique M. , Schneewind Olaf
Published: August 2013

Heritable defects in human B cell/antibody development are not associated with increased susceptibility toStaphylococcus aureusinfection. Protein A (SpA), a surface molecule ofS. aureus, binds the Fcγ domain of immunoglobulin (Ig) and cross-links the Fab domain of VH3-type B cell receptors (IgM). Here we generatedS. aureus spavariants harboring amino acid substitutions at four key residues in each of the five Ig-binding domains of SpA. Wild-typeS. aureusrequired SpA binding to Ig to resist phagocytosis and SpA-mediated B cell receptor cross-linking to block antibody development in mice. ThespaKKAAmutant, which cannot bind Ig or IgM, was phagocytosed and elicited B cell responses to key virulence antigens that protected animals against lethalS. aureuschallenge. The immune evasive attributes ofS. aureusSpA were abolished in µMT mice lacking mature B cells and antibodies. Thus, while wild-typeS. aureusescapes host immune surveillance, thespaKKAAvariant elicits adaptive responses that protect against recurrent infection.

IMPORTANCEStaphylococcus aureuscauses recurrent skin and bloodstream infections without eliciting immunity. Heritable defects in neutrophil and T cell function, but not B cell or antibody development, are associated with increased incidence ofS. aureusinfection, and efforts to develop antibody-basedS. aureusvaccines have thus far been unsuccessful. We show here that the Fcγ and VH3-type Fab binding activities of staphylococcal protein A (SpA) are essential forS. aureusescape from host immune surveillance in mice. The virulence attributes of SpA in mice required mature B cells and immunoglobulin. These results suggest that antibodies and B cells play a key role in the pathogenesis of staphylococcal infections and provide insights into the development of a vaccine againstS. aureus.
Suppression of respiratory papillomatosis with malignant transformation by erlotinib in a kidney transplant recipient
Authors: Hao Zhonglin , Dillard Thomas , Biddinger Paul , Patel Vijay
Published: August 2013

A 52-year-old non-smoker and renal transplant recipient developed an incessant cough. A CT scan of the thorax revealed ill-defined hazy opacities in the right upper lung. He was diagnosed with non-tuberculosisMycobacterium chelonae/abscessusinfection based on sputum culture results. A trial of antibiotics initially resulted in some clinical improvement. A subsequent CT of the thorax documented worsening of the lesions in the right lung and new lesions on the left. An intratracheal growth was noted. Bronchoscopy with biopsy of the tracheal lesions documented respiratory papillomatosis with transformation to squamous cell cancer. Test for high-risk human papilloma virus was positive. Video-assisted thoracoscopic surgery biopsy with wedge resection of the left lower lobe revealed metastatic squamous cell lung cancer. He was treated with one ablation followed by four cycles of chemotherapy. He has been maintained on erlotinib ever since. There has been no recurrence of the cough or papillomas.
Listening to the head and not the heart: subarachnoid haemorrhage associated with severe acute left ventricular failure
Authors: King Christopher
Published: August 2013

Headache is a very common presenting symptom in the emergency department, and distinguishing subarachnoid haemorrhage from more benign causes of headache can be challenging. This particular presentation of subarachnoid haemorrhage was made more difficult by concurrent-related cardiac pathophysiology. This case report describes the evolving differential diagnosis of a 54-year-old woman initially presenting with headache and confusion, with signs and investigations suggestive of ST elevation myocardial infarction and resultant left ventricular failure. The importance of prompt primary percutaenous coronary intervention left clinicians with a difficult decision about which specialty was most appropriate for the patient to be transferred to. Ultimately the symptoms were explained by radiographic confirmation of subarachnoid haemorrhage and subsequent adrenergic storm, causing myocyte injury and myocardial contractile dysfunction. This patient was transferred for coiling of a ruptured cerebral artery berry aneurysm. Her left ventricular failure improved from severe to mild within 48 h of presentation.
Fever, ulcers and joint pain: an incidental finding of oesophageal dysmotility
Authors: Anwuzia-Iwegbu Charles , Fikree Asma , Tufton Nicola
Published: August 2013

A 41-year-old Bangladeshi man presented with a 2-month history of bilateral feet/hand swelling which intermittently resolved without medication. All blood tests performed by the general practitioner (GP) were unremarkable. Following admission to the accident and emergency department, a chest X-ray revealed a ‘vail-like’ opacification in the right side. High-resolution CT confirmed dilation of oesophagus with food debris and circumferential thickening of the lower oesophageal sphincter.
Is the case-mix of patients who self-present to ED similar to general practice and other acute-care facilities?
Authors: Harris Tim , McDonald Keith
Published: August 2013

Objective

To benchmark walk-in presentations to emergency departments (ED) with those presenting to other local acute healthcare facilities.

Setting

A large teaching hospital with an annual ED census of 140 000 adult patients and surrounding associated acute healthcare providers.

Methods

A random sample of 384 patients who self-presented to the ED was obtained. Benchmarking data were drawn from two general practices; the Tower Hamlets Community Services walk-in centre (co-located on-site with the ED) and the GP-run out-of-hours service.

Results

The case-mix presenting to the ED was characterised by a higher proportion of injuries and chest pain, but fewer simple infections and non-traumatic musculoskeletal conditions as compared to other acute care facilities in our region.

Conclusions

Patients with injuries and possible cardiac chest pain were more likely to attend the ED, and those with infection or musculoskeletal problems less likely, as compared with other acute healthcare facilities. The population presenting to the ED is distinct from that presenting to general practice, out-of-hours clinics, or walk-in centres.
CHARGED LEPTON ELECTRIC DIPOLE MOMENT ENHANCEMENT IN THE LORENTZ VIOLATED EXTENSION OF THE STANDARD MODEL
Authors: HAGHIGHAT M. , MOTIE I. , REZAEI Z.
Published: August 2013

We consider the Lorentz violated extension of the standard model. In this framework, there are terms that explicitly violate CP-symmetry. We examine the CPT-even dμν-term to find the electric dipole moment of charged leptons. We show that the form factors besides the momentum transfer, depend on a new Lorentz-scalar, constructing by dμν and the four momenta of the lepton, as well. Such an energy dependence of the electric dipole form factor leads to an enhancement of the lepton electric dipole moment at high energy, even at the zero momentum transfer. We show that at [Formula: see text] the electric dipole moment of the charged lepton can be as large as 10-14 e cm .
PRICING ILLIQUID OPTIONS WITH N + 1 LIQUID PROXIES USING MIXED DYNAMIC-STATIC HEDGING
Authors: HALPERIN IGOR , ITKIN ANDREY
Published: August 2013

We study the problem of the optimal pricing and hedging of a European option written on an illiquid asset Z using a set of proxies: a liquid asset S, and N liquid European options Pi, each written on a liquid asset Yi, i = 1, N. We assume that the S-hedge is dynamic while the multi-name Y-hedge is static. Using the indifference pricing approach with an exponential utility, we derive an HJB equation for the value function, and build an efficient numerical algorithm. The latter is based on several changes of variables, a splitting scheme, and a set of fast Gauss Transforms (FGT), and turns out to be more efficient in terms of complexity and lower local space error than a finite-difference method. While in this paper we apply our framework to an incomplete market version of the credit-equity Merton model, the same approach can be used for other asset classes (equities, commodities, foreign exchange, and so on), for example, for pricing and hedging options with illiquid strikes or illiquid exotic options.
SCHEMES FOR REMOTELY PREPARING AN ARBITRARY FIVE-QUBIT BROWN-TYPE STATE
Authors: MA SONG-YA , TANG PING , LUO MING-XING
Published: August 2013

Two novel schemes via different entanglement resources are put forward to remotely preparing a five-qubit Brown-type state with high probabilities. To design the schemes, some useful measurement bases with the aid of Hurwitz matrix equation are constructed, which have no restrictions on the coefficients of the prepared state. Through a four-particle projective measurement and two-step three-particle projective measurement under the novel sets of mutually orthogonal basis vectors, the remote preparation can be realized with the probability 50% and 100% in general case, respectively. To improve the probability, the special ensembles of the prepared state that the success probability reaches up to 100% are discussed for the first scheme by the permutation group. Furthermore, the present schemes are extended to the nonmaximally entangled quantum channel.
The Gribov phenomenon in flat and curved spaces
Authors: de Cesare Marco
Published: August 2013

The quantization of Yang–Mills theories relies on the gauge-fixing procedure. However, in the non-Abelian case this procedure leads to the well-known Gribov ambiguity. In order to solve the ambiguity a modification of the functional integral formula must be introduced. As a consequence of this, the Green functions get deep modifications in the infrared. We consider, in particular, the SU (N) case and show that in the pure gauge case the ghost propagator is enhanced, while the gluon propagator is suppressed in this limit, therefore the study of the Gribov ambiguity may shed some light on the mass gap problem and on color confinement. We discuss some recent developments on the subject in the case of a curved background. We argue that the concurrent presence of a spacetime curvature and the Gribov ambiguity may introduce further modifications to the Green functions in the infrared.
THE UNIQUENESS OF THE INSTANTANEOUS FREQUENCY BASED ON INTRINSIC MODE FUNCTION
Authors: HUANG NORDEN E. , YOUNG VINCENT , LO MENTZUNG , WANG YUNG HUNG , PENG C. K. , CHEN XIANYAO , WANG GANG , DENG JIA , WU ZHAOHUA
Published: August 2013

It has been claimed that any expression of a(t) cos θ(t) with a(t) as the instantaneous amplitude and cos θ(t) as the carrier varying along with the phase θ(t) could not be uniquely defined. However, based on the fact that a(t) cos θ(t) with all its variational forms have the same numerical value at any given time, we propose the existence of a unique true intrinsic amplitude function ai(t) and phase function θi(t) that ai(t) cos θi(t) satisfying the envelope–carrier relationship is the only expression making physical sense. A constructive method is also presented to find such amplitude-phase pair uniquely from any Intrinsic Mode Function (IMF). As a result, we can treat any IMF in the form of ai(t) cos θi(t) as the unique defined amplitude-phase pair, from which the instantaneous frequency (IF) can also be determined.
Small hysteresis and high energy storage power of antiferroelectric ceramics
Authors: Wang Jinfei , Yang Tongqing , Chen Shengchen , Yao Xi
Published: August 2013

In this paper, modified Pb ( Zr , Ti ) O 3( PZT ) antiferroelectric (AFE) ceramics system was investigated by traditional solid state method. It was observed that the effect of different contents of Zr / Sn , Zr / Ti on modified PZT antiferroelectrics. With increasing Zr / Sn content, the E AFE (electric field of AFE phase to ferroelectric (FE) phase) value was enlarged. The phase switch field was reduced from FE to AFE (E FA ). The hysteresis loops were changed from "slanted" to "square"-types. With increasing Zr / Ti concentrate, the E AFE value, and also the E FA was enlarged, while the hysteresis switch ΔE was reduced. The hysteresis loops was from "square" to "slanted"-types. The samples with square hysteresis loops are suitable for energy storage capacitor applications, the composition of ceramics was Pb 0.97 La 0.02( Zr 0.90 Sn 0.05 Ti 0.05) O 3, which have the largest energy storage density ~ 4.426J/cm3 at 227 kV/cm, and ΔE was ~80 kV/cm, energy efficient η was about 0.612.
Isothermal depolarization current in metal-oxide varistor ceramics under various polarizing fields
Authors: Tonkoshkur Yu. A. , Lyashkov A. Yu. , Tonkoshkur A. S.
Published: August 2013

A method of analysis of experimental kinetic dependences of isothermal depolarization currents in metal-oxide varistor ceramics composed of ZnO – Bi 2 O 3– CoO – Sb 2 O 3– SnO 2– MnO – B 2 O 3 has been proposed and tested. The method is based on reconstruction of dependences with the use of the Kohlrausch–Williams–Watt function. Expansion of the distribution and reduction of the average time of dielectric relaxation of the depolarization were found as the magnitude of the polarizing electric field increased. These findings have been interpreted in the framework of the notion of participation in the recharge of localized states more distant from the Fermi level in the crystallites of zinc-oxide ceramics under increased polarizing fields.
Dissecting Social Cell Biology and Tumors Using Drosophila Genetics
Authors: Pastor-Pareja José Carlos , Xu Tian
Published: August 2013

Cancer was seen for a long time as a strictly cell-autonomous process in which oncogenes and tumor-suppressor mutations drive clonal cell expansions. Research in the past decade, however, paints a more integrative picture of communication and interplay between neighboring cells in tissues. It is increasingly clear as well that tumors, far from being homogenous lumps of cells, consist of different cell types that function together as complex tissue-level communities. The repertoire of interactive cell behaviors and the quantity of cellular players involved call for a social cell biology that investigates these interactions. Research into this social cell biology is critical for understanding development of normal and tumoral tissues. Such complex social cell biology interactions can be parsed in Drosophila. Techniques in Drosophila for analysis of gene function and clonal behavior allow us to generate tumors and dissect their complex interactive biology with cellular resolution. Here, we review recent Drosophila research aimed at understanding tissue-level biology and social cell interactions in tumors, highlighting the principles these studies reveal.