bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental Experiences and Well-Being in Sport: The Importance of the Coaching Climate
Authors: Cronin Lorcan D. , Allen Justine B.
Published: November 2014

The present study explored the relationships between the coaching climate, youth developmental experiences (personal and social skills, cognitive skills, goal setting, and initiative) and psychological well-being (self-esteem, positive affect, and satisfaction with life). In total, 202 youth sport participants (Mage = 13.4, SD = 1.8) completed a survey assessing the main study variables. Findings were consistent with Benson and Saito’s (2001) framework for youth development. In all analyses, the coaching climate was related to personal and social skills, cognitive skills, goal setting, and initiative. Mediational analysis also revealed that the development of personal and social skills mediated the relationships between the coaching climate and all three indices of psychological well-being (self-esteem, positive affect, and satisfaction with life). Interpretation of the results suggests that coaches should display autonomy-supportive coaching behaviors because they are related to the developmental experiences and psychological well-being of youth sport participants.
Black hole lightning due to particle acceleration at subhorizon scales
Authors: Aleksić J. , Ansoldi S. , Antonelli L. A. , Antoranz P. , Babic A. , Bangale P. , Barrio J. A. , González J. Becerra , Bednarek W. , Bernardini E. , Biasuzzi B. , Biland A. , Blanch O. , Bonnefoy S. , Bonnoli G. , Borracci F. , Bretz T. , Carmona E. , Carosi A. , Colin P. , Colombo E. , Contreras J. L. , Cortina J. , Covino S. , Da Vela P. , Dazzi F. , De Angelis A. , De Caneva G. , De Lotto B. , Wilhelmi E. de Oña , Mendez C. Delgado , Prester D. Dominis , Dorner D. , Doro M. , Einecke S. , Eisenacher D. , Elsaesser D. , Fonseca M. V. , Font L. , Frantzen K. , Fruck C. , Galindo D. , López R. J. García , Garczarczyk M. , Terrats D. Garrido , Gaug M. , Godinović N. , Muñoz A. González , Gozzini S. R. , Hadasch D. , Hanabata Y. , Hayashida M. , Herrera J. , Hildebrand D. , Hose J. , Hrupec D. , Idec W. , Kadenius V. , Kellermann H. , Kodani K. , Konno Y. , Krause J. , Kubo H. , Kushida J. , La Barbera A. , Lelas D. , Lewandowska N. , Lindfors E. , Lombardi S. , Longo F. , López M. , López-Coto R. , López-Oramas A. , Lorenz E. , Lozano I. , Makariev M. , Mallot K. , Maneva G. , Mankuzhiyil N. , Mannheim K. , Maraschi L. , Marcote B. , Mariotti M. , Martínez M. , Mazin D. , Menzel U. , Miranda J. M. , Mirzoyan R. , Moralejo A. , Munar-Adrover P. , Nakajima D. , Niedzwiecki A. , Nilsson K. , Nishijima K. , Noda K. , Orito R. , Overkemping A. , Paiano S. , Palatiello M. , Paneque D. , Paoletti R. , Paredes J. M. , Paredes-Fortuny X. , Persic M. , Poutanen J. , Moroni P. G. Prada , Prandini E. , Puljak I. , Reinthal R. , Rhode W. , Ribó M. , Rico J. , Garcia J. Rodriguez , Rügamer S. , Saito T. , Saito K. , Satalecka K. , Scalzotto V. , Scapin V. , Schultz C. , Schweizer T. , Shore S. N. , Sillanpää A. , Sitarek J. , Snidaric I. , Sobczynska D. , Spanier F. , Stamatescu V. , Stamerra A. , Steinbring T. , Storz J. , Strzys M. , Takalo L. , Takami H. , Tavecchio F. , Temnikov P. , Terzić T. , Tescaro D. , Teshima M. , Thaele J. , Tibolla O. , Torres D. F. , Toyama T. , Treves A. , Uellenbeck M. , Vogler P. , Zanin R. , Kadler M. , Schulz R. , Ros E. , Bach U. , Krauß F. , Wilms J.
Published: November 2014

Supermassive black holes with masses of millions to billions of solar masses are commonly found in the centers of galaxies. Astronomers seek to image jet formation using radio interferometry but still suffer from insufficient angular resolution. An alternative method to resolve small structures is to measure the time variability of their emission. Here we report on gamma-ray observations of the radio galaxy IC 310 obtained with the MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov) telescopes, revealing variability with doubling time scales faster than 4.8 min. Causality constrains the size of the emission region to be smaller than 20% of the gravitational radius of its central black hole. We suggest that the emission is associated with pulsar-like particle acceleration by the electric field across a magnetospheric gap at the base of the radio jet.
Immunogenicity of a Bovine Herpesvirus 1 Glycoprotein D DNA Vaccine Complexed with Bovine Neutrophil Beta-Defensin 3
Authors: Mackenzie-Dyck Sarah , Latimer Laura , Atanley Ethel , Kovacs-Nolan Jennifer , Attah-Poku Sam , Babiuk Lorne A. , van Drunen Littel-van den Hurk Sylvia
Published: November 2014

Protective efficacy against bovine herpesvirus 1 (BoHV-1) has been demonstrated to be induced by a plasmid encoding bovine neutrophil beta-defensin 3 (BNBD3) as a fusion construct with truncated glycoprotein D (tgD). However, in spite of the increased cell-mediated immune responses induced by this DNA vaccine, the clinical responses of BoHV-1-challenged cattle were not reduced over those observed in animals vaccinated with the plasmid encoding tgD alone; this might have been because the vaccine failed to improve humoral responses. We hypothesized that an alternative vaccine design strategy that utilized the DNA vaccine pMASIA-tgD as a complex with BNBD3 might improve humoral responses while maintaining robust Th1-type cell-mediated responses. C57BL/6 mice were vaccinated with pMASIA-tgD complexed with 0, 0.01875, 0.1875, or 1.875 nmol of a stable synthesized analog of BNBD3 (aBNBD3). The best results were seen in mice immunized with the vaccine composed of pMASIA-tgD complexed to 0.1875 nmol aBNBD3. In this group, humoral responses were improved, as evidenced by increased virus neutralization, tgD-specific early IgG1, and later IgG2a titers, while the strong cell-mediated immune responses, measured based on specific gamma interferon (IFN-γ)-secreting cells, were maintained relative to pMASIA-tgD. Modulation of the immune response might have been due in part to the effect of BNBD3 on dendritic cells (DCs).In vitrostudies showed that murine bone marrow-derived DCs (BMDCs) pretreated with aBNBD3 were activated, as evidenced by CD11c downregulation, and were functionally mature, as shown by increased allostimulatory ability. Native, synthetic, and analog forms of BNBD3 were equally capable of inducing functional maturation of BMDCs.
Complete Genome Sequence of a Rat Hepatitis E Virus Strain Isolated in the United States
Authors: Debing Yannick , Emerson Suzanne U. , Purcell Robert H. , Neyts Johan , Dallmeier Kai
Published: November 2014

Hepatitis E virus is a common cause of acute hepatitis in humans. Related viruses have been isolated from multiple animal species, including rats, but their impact on human health is unclear. We present the first full-length genome sequence of a rat hepatitis E virus strain isolated in the United States (LA-B350).
Draft Genome Sequence of Pseudomonas aeruginosa ATCC 33988, a Bacterium Highly Adapted to Fuel-Polluted Environments
Authors: Brown Lisa M. , Gunasekera Thusitha S. , Ruiz Oscar N.
Published: November 2014

Pseudomonas aeruginosa
ATCC 33988 is highly adapted to grow in jet and diesel fuel, with a defined regulation of adaptive genes and metabolization of
n
-alkanes. The draft genome of strain ATCC 33988 is 6.4 Mb in size, with 5,975 coding sequences and 66.3% G+C content, and it is highly similar to that of the clinical strain
P. aeruginosa
PAO1.
Genome Sequence of the Lactic Acid Bacterium Lactococcus lactis subsp.
lactis
TOMSC161, Isolated from a Nonscalded Curd Pressed Cheese
Authors: Velly H. , Renault P. , Abraham A.-L. , Loux V. , Delacroix-Buchet A. , Fonseca F. , Bouix M.
Published: November 2014

Lactococcus lactis
is a lactic acid bacterium used in the production of many fermented foods, such as dairy products. Here, we report the genome sequence of
L. lactis
subsp.
lactis
TOMSC161, isolated from nonscalded curd pressed cheese. This genome sequence provides information in relation to dairy environment adaptation.
Draft Genome Sequence of
Rhizobium
sp. H41, a Rock-Weathering Bacterium from a Weathered Rock Surface
Authors: Xi Jun , Sheng Xiafang , He Linyan
Published: November 2014

Rhizobium
sp. H41 isolated from weathered tuff can weather tuff and release Fe, Si, and Al from the rock under nutrient-poor conditions. Here, we report the draft genome sequence of strain H41, which may facilitate a better understanding of the molecular mechanism involved in rock weathering by the bacterium.
Complete Genome Sequence of Cellulophaga lytica HI1 Using PacBio Single-Molecule Real-Time Sequencing
Authors: Asahina Audrey Y. , Hadfield Michael G.
Published: November 2014

We report here the complete genome sequence of
Cellulophaga lytica
HI1 isolated from a seawater table located at the Kewalo Marine Laboratory (Honolulu, HI). This is the first complete
de novo
genome assembly of
C. lytica
HI1 using PacBio single-molecule real-time (SMRT) sequencing, which resulted in a single scaffold of 3.8 Mb.
Detection of Intracellular Parasites by Use of the CellaVision DM96 Analyzer during Routine Screening of Peripheral Blood Smears
Authors: Racsa Lori D. , Gander Rita M. , Southern Paul M. , McElvania TeKippe Erin , Doern Christopher , Luu Hung S.
Published: November 2014

Conventional microscopy is the gold standard for malaria diagnosis. The CellaVision DM96 is a digital hematology analyzer that utilizes neural networks to locate, digitize, and preclassify leukocytes and characterize red blood cell morphology. This study compared the detection rates of
Plasmodium
and
Babesia
species on peripheral blood smears utilizing the CellaVision DM96 with the rates for a routine red blood cell morphology scan. A total of 281 slides were analyzed, consisting of 130 slides positive for
Plasmodium
or
Babesia
species and 151 negative controls. Slides were blinded, randomized, and analyzed by CellaVision and microscopy for red cell morphology scans. The technologists were blinded to prior identification results. The parasite detection rate was 73% (95/130) for CellaVision and 81% (105/130) for microscopy for positive samples. The interobserver agreement between CellaVision and microscopy was fair, as Cohen's kappa coefficient equaled 0.36. Pathologist review of CellaVision images identified an additional 15 slides with parasites, bringing the total number of detectable positive slides to 110 of 130 (85%).
Plasmodium ovale
had the lowest rate of detection at 56% (5 of 9);
Plasmodium malariae
and
Babesia
spp. had the highest rate of detection at 100% (3/3 and 6/6, respectively). The detection rate by CellaVision was 100% (23/23) when the parasitemia was ≥2.5%. The detection rate for <0.1% parasitemia was 63% (15/24). Technologists appropriately classified all negative specimens. The percentage of positive specimens detectable by CellaVision (73%) approaches results for microscopy on routine scan of peripheral blood smears for red blood cell morphology.
High-Resolution Hepatitis C Virus Subtyping Using NS5B Deep Sequencing and Phylogeny, an Alternative to Current Methods
Authors: Quer Josep , Gregori Josep , Rodríguez-Frias Francisco , Buti Maria , Madejon Antonio , Perez-del-Pulgar Sofia , Garcia-Cehic Damir , Casillas Rosario , Blasi Maria , Homs Maria , Tabernero David , Alvarez-Tejado Miguel , Muñoz Jose Manuel , Cubero Maria , Caballero Andrea , delCampo Jose Antonio , Domingo Esteban , Belmonte Irene , Nieto Leonardo , Lens Sabela , Muñoz-de-Rueda Paloma , Sanz-Cameno Paloma , Sauleda Silvia , Bes Marta , Gomez Jordi , Briones Carlos , Perales Celia , Sheldon Julie , Castells Lluis , Viladomiu Lluis , Salmeron Javier , Ruiz-Extremera Angela , Quiles-Pérez Rosa , Moreno-Otero Ricardo , López-Rodríguez Rosario , Allende Helena , Romero-Gómez Manuel , Guardia Jaume , Esteban Rafael , Garcia-Samaniego Javier , Forns Xavier , Esteban Juan Ignacio
Published: November 2014

Hepatitis C virus (HCV) is classified into seven major genotypes and 67 subtypes. Recent studies have shown that in HCV genotype 1-infected patients, response rates to regimens containing direct-acting antivirals (DAAs) are subtype dependent. Currently available genotyping methods have limited subtyping accuracy. We have evaluated the performance of a deep-sequencing-based HCV subtyping assay, developed for the 454/GS-Junior platform, in comparison with those of two commercial assays (Versant HCV genotype 2.0 and Abbott Real-time HCV Genotype II) and using direct NS5B sequencing as a gold standard (direct sequencing), in 114 clinical specimens previously tested by first-generation hybridization assay (82 genotype 1 and 32 with uninterpretable results). Phylogenetic analysis of deep-sequencing reads matched subtype 1 calling by population Sanger sequencing (69% 1b, 31% 1a) in 81 specimens and identified a mixed-subtype infection (1b/3a/1a) in one sample. Similarly, among the 32 previously indeterminate specimens, identical genotype and subtype results were obtained by direct and deep sequencing in all but four samples with dual infection. In contrast, both Versant HCV Genotype 2.0 and Abbott Real-time HCV Genotype II failed subtype 1 calling in 13 (16%) samples each and were unable to identify the HCV genotype and/or subtype in more than half of the non-genotype 1 samples. We concluded that deep sequencing is more efficient for HCV subtyping than currently available methods and allows qualitative identification of mixed infections and may be more helpful with respect to informing treatment strategies with new DAA-containing regimens across all HCV subtypes.
Utility of Measuring (1,3)-β-
d
-Glucan in Cerebrospinal Fluid for Diagnosis of Fungal Central Nervous System Infection
Authors: Lyons Jennifer L. , Thakur Kiran T. , Lee Rick , Watkins Tonya , Pardo Carlos A. , Carson Kathryn A. , Markley Barbara , Finkelman Malcolm A. , Marr Kieren A. , Roos Karen L. , Zhang Sean X.
Published: November 2014

(1-3)-β-
d
-Glucan (BDG) from cerebrospinal fluid (CSF) is a promising marker for diagnostic and prognostic aid of central nervous system (CNS) fungal infection, but its relationship to serum values has not been studied. Herein, we detected BDG from CSF at levels 2-fold lower than those in serum in patients without evidence of fungal disease but 25-fold higher than those in in serum in noncryptococcal CNS fungal infections. CSF BDG may be a useful biomarker in the evaluation of fungal CNS disease.
Comparative Analysis of Subtyping Methods against a Whole-Genome-Sequencing Standard for Salmonella enterica Serotype Enteritidis
Authors: Deng Xiangyu , Shariat Nikki , Driebe Elizabeth M. , Roe Chandler C. , Tolar Beth , Trees Eija , Keim Paul , Zhang Wei , Dudley Edward G. , Fields Patricia I. , Engelthaler David M.
Published: November 2014

A retrospective investigation was performed to evaluate whole-genome sequencing as a benchmark for comparing molecular subtyping methods for
Salmonella enterica
serotype Enteritidis and survey the population structure of commonly encountered
S. enterica
serotype Enteritidis outbreak isolates in the United States. A total of 52
S. enterica
serotype Enteritidis isolates representing 16 major outbreaks and three sporadic cases collected between 2001 and 2012 were sequenced and subjected to subtyping by four different methods: (i) whole-genome single-nucleotide-polymorphism typing (WGST), (ii) multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA), (iii) clustered regularly interspaced short palindromic repeats combined with multi-virulence-locus sequence typing (CRISPR-MVLST), and (iv) pulsed-field gel electrophoresis (PFGE). WGST resolved all outbreak clusters and provided useful robust phylogenetic inference results with high epidemiological correlation. While both MLVA and CRISPR-MVLST yielded higher discriminatory power than PFGE, MLVA outperformed the other methods in delineating outbreak clusters whereas CRISPR-MVLST showed the potential to trace major lineages and ecological origins of
S. enterica
serotype Enteritidis. Our results suggested that whole-genome sequencing makes a viable platform for the evaluation and benchmarking of molecular subtyping methods.
Kinetics of Poliovirus Shedding following Oral Vaccination as Measured by Quantitative Reverse Transcription-PCR versus Culture
Authors: Taniuchi Mami , Begum Sharmin , Uddin Md Jashim , Platts-Mills James A. , Liu Jie , Kirkpatrick Beth D. , Chowdhury Anwarul H. , Jamil Khondoker M. , Haque Rashidul , Petri William A. , Houpt Eric R.
Published: November 2014

Amid polio eradication efforts, detection of oral polio vaccine (OPV) virus in stool samples can provide information about rates of mucosal immunity and allow estimation of the poliovirus reservoir. We developed a multiplex one-step quantitative reverse transcription-PCR (qRT-PCR) assay for detection of OPV Sabin strains 1, 2, and 3 directly in stool samples with an external control to normalize samples for viral quantity and compared its performance with that of viral culture. We applied the assay to samples from infants in Dhaka, Bangladesh, after the administration of trivalent OPV (tOPV) at weeks 14 and 52 of life (on days 0 [pre-OPV], +4, +11, +18, and +25 relative to vaccination). When 1,350 stool samples were tested, the sensitivity and specificity of the quantitative PCR (qPCR) assay were 89 and 91% compared with culture. A quantitative relationship between culture
+
/qPCR
+
and culture
−
/qPCR
+
stool samples was observed. The kinetics of shedding revealed by qPCR and culture were similar. qPCR quantitative cutoffs based on the day +11 or +18 stool samples could be used to identify the culture-positive shedders, as well as the long-duration or high-frequency shedders. Interestingly, qPCR revealed that a small minority (7%) of infants contributed the vast majority (93 to 100%) of the total estimated viral excretion across all subtypes at each time point. This qPCR assay for OPV can simply and quantitatively detect all three Sabin strains directly in stool samples to approximate shedding both qualitatively and quantitatively.
Whole-Genome Phylogenomic Heterogeneity of Neisseria gonorrhoeae Isolates with Decreased Cephalosporin Susceptibility Collected in Canada between 1989 and 2013
Authors: Demczuk Walter , Lynch Tarah , Martin Irene , Van Domselaar Gary , Graham Morag , Bharat Amrita , Allen Vanessa , Hoang Linda , Lefebvre Brigitte , Tyrrell Greg , Horsman Greg , Haldane David , Garceau Richard , Wylie John , Wong Tom , Mulvey Michael R.
Published: November 2014

A large-scale, whole-genome comparison of Canadian
Neisseria gonorrhoeae
isolates with high-level cephalosporin MICs was used to demonstrate a genomic epidemiology approach to investigate strain relatedness and dynamics. Although current typing methods have been very successful in tracing short-chain transmission of gonorrheal disease, investigating the temporal evolutionary relationships and geographical dissemination of highly clonal lineages requires enhanced resolution only available through whole-genome sequencing (WGS). Phylogenomic cluster analysis grouped 169 Canadian strains into 12 distinct clades. While some
N. gonorrhoeae
multiantigen sequence types (NG-MAST) agreed with specific phylogenomic clades or subclades, other sequence types (ST) and closely related groups of ST were widely distributed among clades. Decreased susceptibility to extended-spectrum cephalosporins (ESC-DS) emerged among a group of diverse strains in Canada during the 1990s with a variety of nonmosaic
penA
alleles, followed in 2000/2001 with the
penA
mosaic X allele and then in 2007 with ST1407 strains with the
penA
mosaic XXXIV allele. Five genetically distinct ESC-DS lineages were associated with
penA
mosaic X, XXXV, and XXXIV alleles and nonmosaic XII and XIII alleles. ESC-DS with coresistance to azithromycin was observed in 5 strains with 23S rRNA C2599T or A2143G mutations. As the costs associated with WGS decline and analysis tools are streamlined, WGS can provide a more thorough understanding of strain dynamics, facilitate epidemiological studies to better resolve social networks, and improve surveillance to optimize treatment for gonorrheal infections.
Clinical Outcomes of Enterobacteriaceae Infections Stratified by Carbapenem MICs
Authors: Patel Twisha S. , Nagel Jerod L.
Published: November 2014

The Clinical and Laboratory Standards Institute (CLSI) lowered the MIC breakpoints for meropenem and imipenem from 4 mg/liter to 1 mg/liter for
Enterobacteriaceae
in 2010. The breakpoint change improves the probability of pharmacodynamic target attainment and eliminates the need for microbiology labs to perform confirmatory testing for
Klebsiella pneumoniae
carbapenemase (KPC) production or other beta-lactamases that hydrolyze carbapenems. However, there are limited data evaluating clinical outcomes of the affected breakpoints, and it is unknown if patients infected with
Enterobacteriaceae
with reduced susceptibility are more likely to have poor outcomes when treated with a carbapenem. We conducted a single-center retrospective matched-cohort analysis in adult patients with
Enterobacteriaceae
infections treated with meropenem, imipenem, or doripenem. Patients with
Enterobacteriaceae
infection with a carbapenem MIC of 2 to 8 mg/liter were matched based on pathogen, source of infection, comorbidities, and disease severity (1:1 ratio) to those with a carbapenem MIC of ≤1 mg/liter. A total of 36 patients were included in the study. The group with carbapenem MICs of 2 to 8 mg/liter had a significantly higher 30-day mortality than the group with carbapenem MICs of ≤1 mg/liter (38.9% compared to 5.6%,
P
= 0.04). Total hospital length of stay (LOS) and intensive care unit (ICU) LOS were longer in the group with MICs of 2 to 8 mg/liter than in the group with MICs of ≤1 mg/liter (57.6 days compared to 34.4 days [
P
= 0.06] and 56.6 days compared to 21.7 days [
P
< 0.01], respectively). Patients infected with
Enterobacteriaceae
with a carbapenem MIC of 2, 4, or 8 mg/liter had higher mortality rates and longer ICU LOS than matched cohorts with carbapenem MICs of ≤1 mg/liter, which supports CLSI's recommendation to lower susceptibility breakpoints for carbapenems.
Rotavirus Entry: a Deep Journey into the Cell with Several Exits
Authors: Arias Carlos F. , Silva-Ayala Daniela , López Susana
Published: November 2014

Rotaviruses are the leading etiological agents of acute gastroenteritis in infants and young children worldwide. These nonenveloped viruses enter cells using different types of endocytosis and, depending on the virus strain, travel to different endosomal compartments before exiting to the cytosolic space. In this Gem, we review the viral and cellular factors involved in the different stages of a productive virus cell entry and share with the readers the journey that we have taken into the cell to learn about virus entry.
A Conserved Regulatory Module at the C Terminus of the Papillomavirus E1 Helicase Domain Controls E1 Helicase Assembly
Authors: Schuck Stephen , Stenlund Arne
Published: November 2014

Viruses frequently combine multiple activities into one polypeptide to conserve coding capacity. This strategy creates regulatory challenges to ascertain that the combined activities are compatible and do not interfere with each other. The papillomavirus E1 protein, as many other helicases, has the intrinsic ability to form hexamers and double hexamers (DH) that serve as the replicative DNA helicase. However, E1 also has the more unusual ability to generate local melting by forming a double trimer (DT) complex that can untwist the double-stranded origin of DNA replication (ori) DNA in preparation for DH formation. Here we describe a switching mechanism that allows the papillomavirus E1 protein to form these two different kinds of oligomers and to transition between them. We show that a conserved regulatory module attached to the E1 helicase domain blocks hexamer and DH formation and promotes DT formation. In the presence of the appropriate trigger, the inhibitory effect of the regulatory module is relieved and the transition to DH formation can occur.

IMPORTANCE
This study provides a mechanistic understanding into how a multifunctional viral polypeptide can provide different, seemingly incompatible activities. A conserved regulatory sequence module attached to the AAA
+
helicase domain in the papillomavirus E1 protein allows the formation of different oligomers with different biochemical activities.
Class Switch Recombination and Somatic Hypermutation of Virus-Neutralizing Antibodies Are Not Essential for Control of Friend Retrovirus Infection
Authors: Kato Maiko , Tsuji-Kawahara Sachiyo , Kawasaki Yuri , Kinoshita Saori , Chikaishi Tomomi , Takamura Shiki , Fujisawa Makoto , Kawada Akira , Miyazawa Masaaki
Published: November 2014

Toll-like receptor 7 and Myd88 are required for antiretroviral antibody and germinal center responses, but whether somatic hypermutation and class-switch recombination are required for antiretroviral immunity has not been examined. Mice deficient in activation-induced cytidine deaminase (AID) resisted Friend virus infection, produced virus-neutralizing antibodies, and controlled viremia. Passive transfer demonstrated that immune IgM from AID-deficient mice contributes to Friend virus control in the presence of virus-specific CD4+T cells.
Activation of the Chicken Type I Interferon Response by Infectious Bronchitis Coronavirus
Authors: Kint Joeri , Fernandez-Gutierrez Marcela , Maier Helena J. , Britton Paul , Langereis Martijn A. , Koumans Joseph , Wiegertjes Geert F. , Forlenza Maria
Published: November 2014

Coronaviruses from both the
Alphacoronavirus
and
Betacoronavirus
genera interfere with the type I interferon (IFN) response in various ways, ensuring the limited activation of the IFN response in most cell types. Of the gammacoronaviruses that mainly infect birds, little is known about the activation of the host immune response. We show that the prototypical
Gammacoronavirus
, infectious bronchitis virus (IBV), induces a delayed activation of the IFN response in primary renal cells, tracheal epithelial cells, and a chicken cell line. In fact,
Ifnβ
expression is delayed with respect to the peak of viral replication and the accompanying accumulation of double-stranded RNA (dsRNA). In addition, we demonstrate that MDA5 is the primary sensor for
Gammacoronavirus
infections in chicken cells. Furthermore, we provide evidence that accessory proteins 3a and 3b of IBV modulate the response at the transcriptional and translational levels. Finally, we show that, despite the lack of activation of the IFN response during the early phase of IBV infection, the signaling of nonself dsRNA through both MDA5 and TLR3 remains intact in IBV-infected cells. Taken together, this study provides the first comprehensive analysis of host-virus interactions of a
Gammacoronavirus
with avian innate immune responses.

IMPORTANCE
Our results demonstrate that IBV has evolved multiple strategies to avoid the activation of the type I interferon response. Taken together, the present study closes a gap in the understanding of host-IBV interaction and paves the way for further characterization of the mechanisms underlying immune evasion strategies as well as the pathogenesis of gammacoronaviruses.
Replication of Boid Inclusion Body Disease-Associated Arenaviruses Is Temperature Sensitive in both Boid and Mammalian Cells
Authors: Hepojoki Jussi , Kipar Anja , Korzyukov Yegor , Bell-Sakyi Lesley , Vapalahti Olli , Hetzel Udo
Published: November 2014

Boid inclusion body disease (BIDB) is a fatal disease of boid snakes, the etiology of which has only recently been revealed following the identification of several novel arenaviruses in diseased snakes. BIBD-associated arenaviruses (BIBDAV) are genetically divergent from the classical Old and New World arenaviruses and also differ substantially from each other. Even though there is convincing evidence that BIBDAV are indeed the etiological agent of BIBD, the BIBDAV reservoir hosts—if any exist besides boid snakes themselves—are not yet known. In this report, we use University of Helsinki virus (UHV; a virus that we isolated from a
Boa constrictor
with BIBD) to show that BIBDAV can also replicate effectively in mammalian cells, including human cells, provided they are cultured at 30°C. The infection induces the formation of cytoplasmic inclusion bodies (IB), comprised mainly of viral nucleoprotein (NP), similar to those observed in BIBD and in boid cell cultures. Transferring infected cells from 30°C to 37°C ambient temperature resulted in progressive declines in IB formation and in the amounts of viral NP and RNA, suggesting that BIBDAV growth is limited at 37°C. These observations indirectly indicate that IB formation is linked to viral replication. In addition to mammalian and reptilian cells, UHV infected arthropod (tick) cells when grown at 30°C. Even though our findings suggest that BIBDAV have a high potential to cross the species barrier, their inefficient growth at mammalian body temperatures indicates that the reservoir hosts of BIBDAV are likely species with a lower body temperature, such as snakes.

IMPORTANCE
The newly discovered boid inclusion body disease-associated arenaviruses (BIBDAV) of reptiles have drastically altered the phylogeny of the family
Arenavirus
. Prior to their discovery, known arenaviruses were considered mainly rodent-borne viruses, with each arenavirus species having its own reservoir host. BIBDAV have so far been demonstrated in captive boid snakes, but their possible reservoir host(s) have not yet been identified. Here we show, using University of Helsinki virus as a model, that these viruses are able to infect mammalian (including human) and arthropod cells. Our results provide
in vitro
proof of the considerable ability of arenaviruses to cross species barriers. However, our data indicate that BIBDAV growth occurs at 30°C but is inhibited at 37°C, implying that crossing of the species barrier would be hindered by the body temperature of mammalian species.
Plasmid Partition Mechanisms
Authors: Baxter Jamie C. , Funnell Barbara E.
Published: November 2014

The stable maintenance of low-copy-number plasmids in bacteria is actively driven by partition mechanisms that are responsible for the positioning of plasmids inside the cell. Partition systems are ubiquitous in the microbial world and are encoded by many bacterial chromosomes as well as plasmids. These systems, although different in sequence and mechanism, typically consist of two proteins and a DNA partition site, or prokaryotic centromere, on the plasmid or chromosome. One protein binds site-specifically to the centromere to form a partition complex, and the other protein uses the energy of nucleotide binding and hydrolysis to transport the plasmid, via interactions with this partition complex inside the cell. For plasmids, this minimal cassette is sufficient to direct proper segregation in bacterial cells. There has been significant progress in the last several years in our understanding of partition mechanisms. Two general areas that have developed are (i) the structural biology of partition proteins and their interactions with DNA and (ii) the action and dynamics of the partition ATPases that drive the process. In addition, systems that use tubulin-like GTPases to partition plasmids have recently been identified. In this chapter, we concentrate on these recent developments and the molecular details of plasmid partition mechanisms.
Virulence Plasmids of Spore-Forming Bacteria
Authors: Adams Vicki , Li Jihong , Wisniewski Jessica A. , Uzal Francisco A. , Moore Robert J. , McClane Bruce A. , Rood Julian I.
Published: November 2014

Plasmid-encoded virulence factors are important in the pathogenesis of diseases caused by spore-forming bacteria. Unlike many other bacteria, the most common virulence factors encoded by plasmids in
Clostridium
and
Bacillus
species are protein toxins.
Clostridium perfringens
causes several histotoxic and enterotoxin diseases in both humans and animals and produces a broad range of toxins, including many pore-forming toxins such as
C. perfringens
enterotoxin, epsilon-toxin, beta-toxin, and NetB. Genetic studies have led to the determination of the role of these toxins in disease pathogenesis. The genes for these toxins are generally carried on large conjugative plasmids that have common core replication, maintenance, and conjugation regions. There is considerable functional information available about the unique
tcp
conjugation locus carried by these plasmids, but less is known about plasmid maintenance. The latter is intriguing because many
C. perfringens
isolates stably maintain up to four different, but closely related, toxin plasmids. Toxin genes may also be plasmid-encoded in the neurotoxic clostridia. The tetanus toxin gene is located on a plasmid in
Clostridium tetani
, but the botulinum toxin genes may be chromosomal, plasmid-determined, or located on bacteriophages in
Clostridium botulinum
. In
Bacillus anthracis
it is well established that virulence is plasmid determined, with anthrax toxin genes located on pXO1 and capsule genes on a separate plasmid, pXO2. Orthologs of these plasmids are also found in other members of the
Bacillus cereus
group such as
B. cereus
and
Bacillus thuringiensis
. In
B. thuringiensis
these plasmids may carry genes encoding one or more insecticidal toxins.
Current primary care management of children aged 1–36 months with urinary tract infections in Europe: large scale survey of paediatric practice
Authors: Hadjipanayis Adamos , Grossman Zachi , del Torso Stefano , van Esso Diego , Dornbusch Hans Juergen , Mazur Artur , Drabik Anna , Montini Giovanni
Published: November 2014

Objective

To describe current practice among European paediatricians regarding diagnosis and management of urinary tract infections in children aged 1–36 months and to compare these practices with recently published guidelines.

Design

Web-based large scale survey evaluating knowledge of, attitudes towards and the methods for diagnosing, treating and managing urinary tract infections in children.

Setting

Primary and secondary care practices in Europe.

Sample

1129 paediatricians.

Results

A diagnosis of urinary tract infection is considered by 62% of the respondents in children aged 1–36 months with unexplained fever. The preferred method of urine collection is use of a bag (53% for infants <3 months and 59% for children 4–36 months of age). 60% of paediatricians agree that oral and parenteral antibiotics have equal efficacy. Co-amoxiclav is the antibiotic of choice for 41% of participants, while 9% prescribe amoxicillin. 80% of respondents prescribe ultrasound in all children with a confirmed urinary tract infection. 63% of respondents prescribe a cystography when abnormalities are revealed during ultrasound evaluation. A quarter of respondents recommend antibiotic prophylaxis for all children with any vesicoureteral reflux. The data among European countries are very heterogeneous. The three most recent urinary tract infection guidelines (the National Institute for Health and Care Excellence (NICE), the American Academy of Paediatrics and the Italian Society of Paediatric Nephrology) are not followed properly.

Conclusions

Management of febrile urinary tract infections remains controversial and heterogeneous in Europe. Simple, short, practical and easy-to-remember guidelines and educational strategies to ensure their implementation should be developed.
Active management of food allergy: an emerging concept
Authors: Anagnostou Katherine , Stiefel Gary , Brough Helen , du Toit George , Lack Gideon , Fox Adam T
Published: November 2014

IgE-mediated food allergies are common and currently there is no cure. Traditionally, management has relied upon patient education, food avoidance and the provision of an emergency medication plan. Despite this, food allergy can significantly impact on quality of life. Therefore, in recent years, evolving research has explored alternative management strategies. A more active approach to management is being adopted, which includes early introduction of potentially allergenic foods, anticipatory testing, active monitoring, desensitisation to food allergens and active risk management. This review will discuss these areas in turn.
Case fatality rate and associated factors in patients with 22q11 microdeletion syndrome: a retrospective cohort study
Authors: Repetto Gabriela M , Guzmán M Luisa , Delgado Iris , Loyola Hugo , Palomares Mirta , Lay-Son Guillermo , Vial Cecilia , Benavides Felipe , Espinoza Karena , Alvarez Patricia
Published: November 2014

Objective

Chromosome 22q11.2 deletion is the most commonly occurring known microdeletion syndrome. Deaths related to the syndrome have been reported, but the magnitude of death has not been quantified. This study evaluated the deletion's impact on survival and its clinical manifestations in a large cohort of Chilean patients.

Design

Demographic and clinical data of individuals with 22q11 deletions diagnosed between 1998 and 2013 were collected from medical records and death certificates. Case fatality rate was calculated and compared with national vital statistics. OR with 95% CI analysis was used to assess the association between clinical manifestations and death.

Setting

Genetic services in tertiary care centres in Chile, following patients with 22q11.2 deletion.

Outcomes

Fatality rate and associated factors.

Results

59 of 419 patients (14.1%) died during the study period at a median of 3.4 months (range 0 to 32 years of age). Factors associated with death included congenital heart disease (OR 5.27; 95% CI 2.06 to 13.99; p<0.0001), hypocalcaemia (OR 4.27; 95% CI 1.67 to 11.15; p<0.002) and airway malacia (OR 13.37; 95% CI 1.19 to 110.51; p<0.002). Patients with deletions and defects such as tetralogy of Fallot with or without pulmonary atraesia, truncus arteriosus or ventricular septal defect, had a 2.6-fold to 4.6-fold higher death rate compared with nationwide reports for the same types of defects.

Conclusions

In this cohort, we observed a death rate of 14.1%, implying that one in seven patients with 22q11 deletion died during the study period. Significant associations with cardiac defects, hypocalcaemia and airway malacia were observed. Furthermore, the death risk in patients with 22q11 deletion and cardiac defects exceeded the global figures observed in Chile for infants with structurally similar but apparently isolated anomalies. These observations indicate a need to identify patients who may require specific perioperative management to improve survival.
Objectively-assessed and self-reported sedentary time in relation to multiple socioeconomic status indicators among adults in England: a cross-sectional study
Authors: Stamatakis Emmanuel , Coombs Ngaire , Rowlands Alex , Shelton Nicola , Hillsdon Melvyn
Published: November 2014

Objectives

To examine the associations between socioeconomic position (SEP) and multidomain self-reported and objectively-assessed sedentary time (ST).

Design

Cross-sectional.

Setting

General population households in England.

Participants

2289 adults aged 16–96 years who participated in the 2008 Health Survey for England.

Outcomes

Accelerometer-measured ST, and self-reported television time, non-television leisure-time sitting and occupational sitting/standing. We examined multivariable associations between household income, social class, education, area deprivation for each SEP indicator (including a 5-point composite SEP score computed by aggregating individual SEP indicators) and each ST indicator using generalised linear models.

Results

Accelerometry-measured total ST and occupational sitting/standing were positively associated with SEP score and most of its constituent SEP indicators, while television time was negatively associated with SEP score and education level. Area-level deprivation was largely unrelated to ST. Those in the lowest composite SEP group spent 64 (95% CIs 52 to 76) and 72 (48 to 98), fewer minutes/day in total ST and occupational sitting/standing compared to those in the top SEP group, and an additional 48 (35–60) min/day watching television (p<0.001 for linear trend). Stratified analyses showed that these associations between composite SEP score and total ST were evident only among participants who were in employment.

Conclusions

Occupational sitting seems to drive the positive association between SEP and total ST. Lower SEP is linked to higher TV viewing times.
Antibiotic prescribing in long-term care facilities: a qualitative, multidisciplinary investigation
Authors: Fleming Aoife , Bradley Colin , Cullinan Shane , Byrne Stephen
Published: November 2014

Objectives

To explore healthcare professionals’ views of antibiotic prescribing in long-term care facilities (LTCFs). To use the findings to recommend intervention strategies for antimicrobial stewardship in LTCFs.

Design

Qualitative semistructured interviews were conducted. The data were analysed by thematic content analysis. After the interviews, the emerging findings were mapped to the theoretical domains framework (TDF), and the behaviour change wheel and behaviour change technique (BCT) taxonomy were used to recommend future intervention strategies.

Participants

Interviews were conducted with 37 healthcare professionals who work in LTCFs (10 general practitioners, 4 consultants, 14 nurses, 9 pharmacists) between December 2012 and March 2013.

Setting

Interviews were conducted in the greater Cork region.

Results

The main domains from the TDF which emerged were: ‘Knowledge’, ‘Environmental context and resources’, ‘Social influences’, ‘Beliefs about consequences’, ‘Memory, attention and decision making’, with the findings identifying a need for ‘Behavioural regulation’. Many participants believed that antibiotic prescribing was satisfactory at their LTCF, despite the lack of surveillance activities.

Conclusions

This study, using the TDF and BCT taxonomy, has found that antibiotic prescribing in LTCFs is influenced by many social and contextual factors. The challenges of the setting and patient population, the belief about consequences to the patient, and the lack of implementation of guidelines and knowledge regarding antibiotic prescribing patterns are significant challenges to address. On the basis of the study findings and the application of the TDF and BCT taxonomy, we suggest some practical intervention functions for antimicrobial stewardship in LTCFs.
ERG expression in chondrogenic bone and soft tissue tumours
Authors: Shon Wonwoo , Folpe Andrew L , Fritchie Karen J
Published: November 2014

Aim

We studied ERG expression in a large series of chondrogenic bone and soft tissue tumours to assess the value of ERG as a possible marker of chondroid/cartilaginous differentiation.

Methods

Formalin-fixed, paraffin-embedded whole sections from 111 bone and soft tissue tumours with chondroid differentiation or a morphology that may mimic cartilaginous differentiation were retrieved. Immunohistochemistry was performed using anti-ERG monoclonal antibody directed against the N terminus. Nuclear staining was scored as negative (<5%), 1+ (5%–25%), 2+ (26%–50%), 3+ (>51%).

Results

Nuclear ERG expression was seen in all cases of soft tissue chondroma (8), chondromyxoid fibroma (7), chondroblastic osteosarcoma (6) and clear cell chondrosarcoma (1). 10/12 conventional chondrosarcomas were also positive for ERG. In cases of dedifferentiated chondrosarcoma, the well-differentiated component was positive in 7/9 cases, while all dedifferentiated foci were negative. In cases of mesenchymal chondrosarcoma, the hyaline cartilage component was positive in 2/4 cases, whereas the primitive component in all cases was negative. Variable positivity was identified in extraskeletal myxoid chondrosarcomas (4/9), chondroblastomas (3/8) and mixed tumours/myoepitheliomas (2/11). Only 1/12 chordoma was positive for ERG (1+). Interestingly, 15/17 enchondromas were negative for ERG.

Conclusions

In this study, we further characterise the expression of ERG in mesenchymal tumours and found relatively constant nuclear ERG expression in selected chondrogenic tumours including conventional chondrosarcoma, chondromyxoid fibroma, chondroblastic osteosarcoma and clear cell chondrosarcoma. We also show that ERG may be a helpful ancillary tool in certain select diagnostic scenarios and that awareness of ERG expression in tumours with cartilaginous differentiation is important.
Blood-based candidate biomarkers of the presence of neuropsychiatric systemic lupus erythematosus in children
Authors: Brunner Hermine I , Klein-Gitelman Marisa S , Zelko Frank , Beebe Dean W , Foell Dirk , Lee Jiha , Zaal Ahmad , Jones Jordan , Roebuck-Spencer Tresa , Ying Jun
Published: November 2014

Objective

To examine select brain-reactive proteins for their usefulness to serve as blood-based biomarkers in the screening for neurocognitive deficits in childhood-onset systemic lupus erythematosus (cSLE-NCD).

Methods

Patients withcSLE (n=40) were studied longitudinally (month 1; month 18): working memory, psychomotor speed and visuoconstructional ability were assessed using formal neurocognitive testing to determine the presence of cSLE-NCD. Patients also completed the computerised Paediatric Automated Neuropsychological Assessment Metrics. The following brain-reactive proteins were measured in the blood: neutrophil gelatinase associated lipocalin (NGAL), S100B, S100A8/9, antibodies to NR2 glutamate receptor (aNR2-AB), ribosomal-P (aP-AB), glycoprotein-1 (aGP1-AB), and lupus anticoagulant.

Results

cSLE-NCD was present in 6 of 40 patients at baseline and 4 of 27 patients with 18-month information. aP-AB positivity was more commonly present with cSLE-NCD than without (p=0.05). aP-ABs were negatively associated with performance on tests assessing working memory, psychomotor speed and visuoconstructional ability in using formal neurocognitive testing. There were also significant negative associations between aP-AB, S100A8/9, aNR2-AB, aGP1-AB, and lupus anticoagulant and accuracy rates on select Paediatric Automated Neuropsychological Assessment Metrics subtests (p<0.05). Over time, decline in cognitive performance was more pronounced among patients with higher NGAL and aNR2-AB levels. Combinations of serum levels of S100A8/9, S100B, NGAL, aNR2-AB and aP-AB were able to identify cSLE-NCD (sensitivity: 100%; specificity 76%) in exploratory analysis.

Conclusions

Select brain-reactive proteins in the blood are associated with cognitive performance and the presence of cSLE-NCD, cross-sectionally and over time. This raises the possibility that testing of these proteins may assist with the screening of cSLE-NCD.
The Lazarus Funnel: a blinded prospective randomized in vitro trial of a novel CE-marked thrombectomy assist device
Authors: Fargen Kyle M , Mocco J , Gobin Y Pierre
Published: November 2014

Introduction

The use of retrievable stents for acute ischemic stroke (AIS) may result in the release of distal emboli in 12–22% of cases. The Lazarus Funnel is a novel CE-marked thrombectomy assist device designed to capture the stentriever and thrombus to minimize the likelihood of distal embolization. To study this technology, we performed a randomized blinded in vitro evaluation of this device.

Methods

A cerebral flow model was used as an in vitro simulator for cerebral arterial thrombectomy procedures. Stratified block randomization was performed following embolus injection into one of three cohorts: Solitaire stentriever plus guide catheter (control); control plus proximal Funnel placement; or control plus distal Funnel placement. Time to embolectomy, recanalization, and incidence of distal emboli were determined by a blinded observer.

Results

Forty-five thrombectomy trials were performed (15 in each group). The average time required for thrombectomy in each group was 8 min 26 s, 11 min 0 s and 9 min 24 s, respectively (p=NS). Use of the Funnel was associated with significantly improved recanalization compared with stentriever alone (p<0.01). Use of the proximal Funnel resulted in a 25% increase in successful recanalization and a 20% reduction in distal emboli. Use of the distal Funnel resulted in a 200% increase in successful recanalization and a 60% reduction in emboli.

Conclusions

In this AIS embolism flow model with Solitaire thrombectomy, the Lazarus Funnel resulted in a significant increase in recanalization and significant reduction in distal emboli without increase in time to recanalization.