bluuebunny/crossref_metadata_2025_split huggingface dataset:
Male-Specific W4P/R Mutation in the Pre-S1 Region of Hepatitis B Virus, Increasing the Risk of Progression of Liver Diseases in Chronic Patients
Authors: Lee Seoung-Ae , Kim Ki-Jeong , Kim Dong-Won , Kim Bum-Joon 
Published: September 2013

ABSTRACT

The issue of hepatitis B virus (HBV) mutations possibly leading to a gender disparity in the progression of liver diseases has not been explored. We aimed to elucidate the relationships of the novel
pre-S1
mutations, W4P/R, with the progression of liver diseases and male predominance in a South Korean chronic cohort by use of a molecular epidemiologic study. We developed a fluorescence resonance energy transfer (FRET)-based real-time PCR (RT-PCR) assay for the detection of the W4P/R mutations and applied it to 292 chronic HBV patients. The
pre-S1
mutations from 247 (84.6%) of a total of 292 patients were detected by this assay. W4P/R mutants were found to be significantly related to severe liver diseases (hepatocellular carcinoma [HCC] and liver cirrhosis, 12.4% [19/153] of patients, versus chronic hepatitis and asymptomatic carriage, 1.1% [1/94] of patients) (
P
< 0.001). All of the W4P/R mutants were found in males only. The novel HBV
pre-S1
mutations, W4P/R, may be associated with disease severity in male patients chronically infected with HBV genotype C. The W4P/R mutations may provide in part an explanation for the relatively high ratio of male to female incidence in HCC generation in South Korean chronic HBV patients.
International Multicenter Evaluation of the DiversiLab Bacterial Typing System for Escherichia coli and Klebsiella spp
Authors: Voets Guido M. , Leverstein-van Hall Maurine A. , Kolbe-Busch Susanne , van der Zanden Adri , Church Deirdre , Kaase Martin , Grisold Andrea , Upton Mathew , Cloutman-Green Elaine , Cantón Rafael , Friedrich Alexander W. , Fluit Ad C. 
Published: September 2013

ABSTRACT

Successful multidrug-resistant clones are increasing in prevalence globally, which makes the ability to identify these clones urgent. However, adequate, easy-to-perform, and reproducible typing methods are lacking. We investigated whether DiversiLab (DL), an automated repetitive-sequence-based PCR bacterial typing system (bioMérieux), is suitable for comparing isolates analyzed at different geographic centers. A total of 39
Escherichia coli
and 39
Klebsiella
species isolates previously typed by the coordinating center were analyzed. Pulsed-field gel electrophoresis (PFGE) confirmed the presence of one cluster of 6 isolates, three clusters of 3 isolates, and three clusters of 2 isolates for each set of isolates. DL analysis was performed in 11 centers in six different countries using the same protocol. The DL profiles of 425
E. coli
and 422
Klebsiella
spp. were obtained. The DL system showed a lower discriminatory power for
E. coli
than did PFGE. The local DL data showed a low concordance, as indicated by the adjusted Rand and Wallace coefficients (0.132 to 0.740 and 0.070 to 1.0 [
E. coli
] and 0.091 to 0.864 and 0.056 to 1.0 [
Klebsiella
spp.], respectively). The central analysis showed a significantly improved concordance (0.473 to 1.0 and 0.290 to 1.0 [
E. coli
] and 0.513 to 0.965 and 0.425 to 1.0 [
Klebsiella
spp.], respectively). The misclassifications of profiles for individual isolates were mainly due to inconsistent amplification, which was most likely due to variations in the quality and amounts of the isolated DNA used for amplification. Despite local variations, the DL system has the potential to indicate the occurrence of clonal outbreaks in an international setting, provided there is strict adherence to standardized, reproducible DNA isolation methods and analysis protocols, all supported by a central database for profile comparisons.
Dissociation of Prion Protein Amyloid Seeding from Transmission of a Spongiform Encephalopathy
Authors: Piccardo Pedro , King Declan , Telling Glenn , Manson Jean C. , Barron Rona M. 
Published: September 2013

ABSTRACT

Misfolding and aggregation of proteins are common pathogenic mechanisms of a group of diseases called proteinopathies. The formation and spread of proteinaceous lesions within and between individuals were first described in prion diseases and proposed as the basis of their infectious nature. Recently, a similar “prion-like” mechanism of transmission has been proposed in other neurodegenerative diseases such as Alzheimer's disease. We investigated if misfolding and aggregation of corrupted prion protein (PrP
TSE
) are always associated with horizontal transmission of disease. Knock-in transgenic mice (101LL) expressing mutant PrP (PrP-101L) that are susceptible to disease but do not develop any spontaneous neurological phenotype were inoculated with (i) brain extracts containing PrP
TSE
from healthy 101LL mice with PrP plaques in the corpus callosum or (ii) brain extracts from mice overexpressing PrP-101L with neurological disease, severe spongiform encephalopathy, and formation of proteinase K-resistant PrP
TSE
. In all instances, 101LL mice developed PrP plaques in the area of inoculation and vicinity in the absence of clinical disease or spongiform degeneration of the brain. Importantly, 101LL mice did not transmit disease on serial passage, ruling out the presence of subclinical infection. Thus, in both experimental models the formation of PrP
TSE
is not infectious. These results have implications for the interpretation of tests based on the detection of protein aggregates and suggest that
de novo
formation of PrP
TSE
in the host does not always result in a transmissible prion disease. In addition, these results question the validity of assuming that all diseases due to protein misfolding can be transmitted between individuals.
Analysis of Borna Disease Virus Trafficking in Live Infected Cells by Using a Virus Encoding a Tetracysteine-Tagged P Protein
Authors: Charlier Caroline M. , Wu Yuan-Ju , Allart Sophie , Malnou Cécile E. , Schwemmle Martin , Gonzalez-Dunia Daniel 
Published: September 2013

ABSTRACT
Borna disease virus (BDV) is a nonsegmented, negative-stranded RNA virus characterized by noncytolytic persistent infection and replication in the nuclei of infected cells. To gain further insight on the intracellular trafficking of BDV components during infection, we sought to generate recombinant BDV (rBDV) encoding fluorescent fusion viral proteins. We successfully rescued a virus bearing a tetracysteine tag fused to BDV-P protein, which allowed assessment of the intracellular distribution and dynamics of BDV using real-time live imaging. In persistently infected cells, viral nuclear inclusions, representing viral factories tethered to chromatin, appeared to be extremely static and stable, contrasting with a very rapid and active trafficking of BDV components in the cytoplasm. Photobleaching (fluorescence recovery after photobleaching [FRAP] and fluorescence loss in photobleaching [FLIP]) imaging approaches revealed that BDV components were permanently and actively exchanged between cellular compartments, including within viral inclusions, albeit with a fraction of BDV-P protein not mobile in these structures, presumably due to its association with viral and/or cellular proteins. We also obtained evidence for transfer of viral material between persistently infected cells, with routing of the transferred components toward the cell nucleus. Finally, coculture experiments with noninfected cells allowed visualization of cell-to-cell BDV transmission and movement of the incoming viral material toward the nucleus. Our data demonstrate the potential of tetracysteine-tagged recombinant BDV for virus tracking during infection, which may provide novel information on the BDV life cycle and on the modalities of its interaction with the nuclear environment during viral persistence.
Densovirus Crosses the Insect Midgut by Transcytosis and Disturbs the Epithelial Barrier Function
Authors: Wang Y. , Gosselin Grenet A. S. , Castelli I. , Cermenati G. , Ravallec M. , Fiandra L. , Debaisieux S. , Multeau C. , Lautredou N. , Dupressoir T. , Li Y. , Casartelli M. , Ogliastro M. 
Published: September 2013

ABSTRACT

Densoviruses are parvoviruses that can be lethal for insects of different orders at larval stages. Although the horizontal transmission mechanisms are poorly known, densoviral pathogenesis usually starts with the ingestion of contaminated food by the host. Depending on the virus, this leads to replication restricted to the midgut or excluding it. In both cases the success of infection depends on the virus capacity to enter the intestinal epithelium. Using the
Junonia coenia
densovirus (JcDNV) as the prototype virus and the lepidopteran host
Spodoptera frugiperda
as an interaction model, we focused on the early mechanisms of infection during which JcDNV crosses the intestinal epithelium to reach and replicate in underlying target tissues. We studied the kinetics of interaction of JcDNV with the midgut epithelium and the transport mechanisms involved. Using several approaches,
in vivo
,
ex vivo
, and
in vitro
, at molecular and cellular levels, we show that JcDNV is specifically internalized by endocytosis in absorptive cells and then crosses the epithelium by transcytosis. As a consequence, viral entry disturbs the midgut function. Finally, we showed that four mutations on the capsid of JcDNV affect specific recognition by the epithelial cells but not their binding.
Direct Formation of Vaccinia Virus Membranes from the Endoplasmic Reticulum in the Absence of the Newly Characterized L2-Interacting Protein A30.5
Authors: Maruri-Avidal Liliana , Weisberg Andrea S. , Moss Bernard 
Published: September 2013

ABSTRACT
Crescents consisting of a single lipoprotein membrane with an external protein scaffold comprise the initial structural elements of poxvirus morphogenesis. Crescents enlarge to form spherical immature virions, which enclose viroplasm consisting of proteins destined to form the cores of mature virions. Previous studies suggest that the L2 protein participates in the recruitment of endoplasmic reticulum (ER)-derived membranes to form immature virions within assembly sites of cytoplasmic factories. Here we show that L2 interacts with the previously uncharacterized 42-amino-acid A30.5 protein. An open reading frame similar in size to the one encoding A30.5 is at the same genome location in representatives of all chordopoxvirus genera. A30.5 has a putative transmembrane domain and colocalized with markers of the endoplasmic reticulum and with L2. By constructing a complementing cell line expressing A30.5, we isolated a deletion mutant virus that exhibits a defect in morphogenesis in normal cells. Large electron-dense cytoplasmic inclusions and clusters of scaffold protein-coated membranes that resemble crescents and immature virions devoid of viroplasm were seen in place of normal structures. Crescent-shaped membranes were continuous with the endoplasmic reticulum membrane and oriented with the convex scaffold protein-coated side facing the lumen, while clusters of completed spherical immature-virion-like forms were trapped within the expanded lumen. Immature-virion-like structures were more abundant in infected RK-13 cells than in BS-C-1 or HeLa cells, in which cytoplasmic inclusions were decorated with scaffold protein-coated membrane arcs. We suggest that the outer surface of the poxvirus virion is derived from the luminal side of the ER membrane.
Human H7N9 Influenza A Viruses Replicate in Swine Respiratory Tissue Explants
Authors: Jones J. C. , Baranovich T. , Zaraket H. , Guan Y. , Shu Y. , Webby R. J. , Webster R. G. 
Published: September 2013

ABSTRACT
Recently, novel H7N9 influenza viruses have caused an unprecedented outbreak in humans. Pigs are an important intermediate host for influenza; thus, we assessed the replication ability of three human H7N9 viruses (A/Anhui/1/2013, A/Shanghai/1/2013, A/Shanghai/2/2013) in swine tissue explants. All viruses tested replicated efficiently in explants from tracheas and bronchi, with limited replication in alveolar cells. Swine respiratory tissue explants can serve as an efficient model for screening replication potential of newly emerging H7N9 viruses.
Analysis of the quantity and quality of published randomised controlled trials related to injury prevention from 2001 to 2010 in China
Authors: He Qiong , Kang Wenjing , Tian Danping , Huang Yuanxiu , Gao Lin , Deng Xin , Li Li , Hu Guoqing 
Published: September 2013

ObjectiveTo report the quantity and quality of published randomised controlled trails (RCT) on injury prevention in China.DesignBibliometric analysis.SettingChina, 2001–2010.Data sourcesThe published RCTs that were indexed by four domestic electronic databases and two international databases between 1 January 2001 and 31 December 2010.Main outcome measuresNumbers and proportions of published RCTs and those that did not report or specify the quality items recommended by Cochrane Handbook for Systematic Reviews of Intervention V.5.0.0.ResultsOf 4834 publications of injury prevention, 25 RCTs with 55 431 participants were identified. One study had no full text. Twenty-three RCTs were published in Chinese language. All 25 studies chose education as the intervention, including 19 studies using education as single intervention and 6 studies using education as a part of combined intervention. Eighteen of 19 studies that used injury incidence rate as the primary outcome measure; 10 studies reported 24–59% reductions in injury incidence rate in the intervention group, and 8 studies reported 24–76% rate difference between the intervention group and the control group after the implementation of intervention. Only 1 study reported no significant difference. The other 6 studies only reported improvements in knowledge, attitude and practice/behaviour. None of 24 studies with full text included the information of ‘allocation concealment’, ‘blinding’ and ‘free of early stopping bias’.ConclusionsThe value of 25 published RCTs cannot be determined due to the lack of quality information. More high-quality RCTs need to be performed in the future.
The golden hour of stroke intervention: effect of thrombectomy procedural time in acute ischemic stroke on outcome
Authors: Spiotta Alejandro M , Vargas Jan , Turner Raymond , Chaudry M Imran , Battenhouse Holly , Turk Aquilla S 
Published: September 2013

IntroductionOutcome studies in acute ischemic stroke (AIS) have focused on time from symptom onset to treatment. The purpose of this study was to investigate whether time to achieve vessel recanalization from groin puncture affects outcomes.MethodsWe studied all AIS cases that underwent intra-arterial therapy between May 2008 and October 2012 at a high volume center for anterior circulation occlusions. Candidacy for thrombectomy is determined by CT perfusion imaging, irrespective of time of onset. Patients were then dichotomized into two groups: ‘Early recan’ assigned in which recanalization was achieved in ≤60 min from groin puncture and ‘Delayed recan’ in which procedures extended beyond 60 min. Time to recanalize was also studied as a continuous variable.Results159 patients (53.5% women, mean age 66.4±15.2 years) were identified. The mean National Institutes of Health Stroke Scale (NIHSS) score was similar between ‘Early recan’ patients (16.8±6.1) compared with ‘Delayed recan’ patients (15.4±5.8, p=0.149). Among the ‘Early recan’ patients, recanalization was achieved in 40.7±13.6 min compared with 101.7±32.5 min in the ‘Delayed recan’ patients (p<0.0001). The likelihood of achieving a good outcome (modified Rankin Scale score 0–2) was higher in the ‘Early recan’ group (53.6%) compared with the ‘Late recan’ group (30.8%; p=0.009). On logistic regression analysis, time to recanalization from groin puncture, baseline NIHSS, revascularization, diabetes, and hemorrhages were found to significantly impact on outcome at 90 days, as measured by the modified Rankin Scale.ConclusionsOur findings suggest that extending mechanical thrombectomy procedure times beyond 60 min increases complications and device cost rates while worsening outcomes. These findings can serve as a time frame of when it is prudent to abort a failed thrombectomy case.
Targeting of NAD Metabolism in Pancreatic Cancer Cells: Potential Novel Therapy for Pancreatic Tumors
Authors: Chini Claudia C.S. , Guerrico Anatilde M. Gonzalez , Nin Veronica , Camacho-Pereira Juliana , Escande Carlos , Barbosa Maria Thereza , Chini Eduardo N. 
Published: September 2013

Abstract
Purpose: Here, we describe a novel interplay between NAD synthesis and degradation involved in pancreatic tumor growth.
Experimental Design: We used human pancreatic cancer cells, both in vitro (cell culture experiments) and in vivo (xenograft experiments), to demonstrate the role of NAD synthesis and degradation in tumor cell metabolism and growth.
Results: We demonstrated that pharmacologic and genetic targeting of Nampt, the key enzyme in the NAD salvage synthesis pathway, inhibits cell growth and survival of pancreatic cancer cells. These changes were accompanied by a reduction of NAD levels, glycolytic flux, lactate production, mitochondrial function, and levels of ATP. The massive reduction in overall metabolic activity induced by Nampt inhibition was accompanied by a dramatic decrease in pancreatic tumor growth. The results of the mechanistic experiments showed that neither the NAD-dependent enzymes PARP-1 nor SIRT1 play a significant role on the effect of Nampt inhibition on pancreatic cancer cells. However, we identified a role for the NAD degradation pathway mediated by the NADase CD38 on the sensitivity to Nampt inhibition. The responsiveness to Nampt inhibition is modulated by the expression of CD38; low levels of this enzyme decrease the sensitivity to Nampt inhibition. In contrast, its overexpression decreased cell growth in vitro and in vivo, and further increased the sensitivity to Nampt inhibition.
Conclusions: Our study demonstrates that NAD metabolism is essential for pancreatic cancer cell survival and proliferation and that targeting NAD synthesis via the Nampt pathway could lead to novel therapeutic treatments for pancreatic cancer. Clin Cancer Res; 20(1); 120–30. ©2013 AACR.
Tetrahydrobiopterin Determines Vascular Remodeling Through Enhanced Endothelial Cell Survival and Regeneration
Authors: Ali Ziad A. , Rinze Ruth , Douglas Gillian , Hu Yanhua , Xiao Qingzhong , Qi Wei , McNeill Eileen , Bursill Christina , George Isaac , Greaves David R. , Xu Qingbo , Channon Keith M. 
Published: September 2013

Background—
Endothelial cell (EC) survival and regeneration are important determinants of the response to vascular injury that leads to neointimal hyperplasia and accelerated atherosclerosis. Nitric oxide (NO) is a key regulator of EC and endothelial progenitor cell function, but the pathophysiological mechanisms that regulate endothelial NO synthase in endothelial regeneration remain unclear.

Methods and Results—
Endothelium-targeted overexpression of GTP cyclohydrolase (GCH) I increased levels of the endothelial NO synthase cofactor, tetrahydrobiopterin, in an EC-specific manner and reduced neointimal hyperplasia in experimental vein grafts in GCH/apolipoprotein E-knockout mice. These effects were mediated through enhanced donor-derived survival and recipient-derived repopulation of GCH transgenic ECs, revealed by tracking studies in Tie2-LacZ/GCH-Tg/apolipoprotein E-knockout recipient mice or donor grafts, respectively. Endothelial GCH overexpression increased endothelial NO synthase coupling and enhanced the proliferative capacity of ECs and circulating endothelial progenitor cell numbers after vascular injury.

Conclusions—
These observations indicate that endothelial tetrahydrobiopterin availability modulates neointimal hyperplasia after vascular injury via accelerated EC repopulation and growth. Targeting tetrahydrobiopterin-dependent endothelial NO synthase regulation in the endothelium is a rational therapeutic target to enhance endothelial regeneration and reduce neointimal hyperplasia in vascular injury states.
Monitoring of Monocyte Recruitment in Reperfused Myocardial Infarction With Intramyocardial Hemorrhage and Microvascular Obstruction by Combined Fluorine 19 and Proton Cardiac Magnetic Resonance Imaging
Authors: Ye Yu-Xiang , Basse-Lüsebrink Thomas C. , Arias-Loza Paula-Anahi , Kocoski Vladimir , Kampf Thomas , Gan Qiang , Bauer Elisabeth , Sparka Stefanie , Helluy Xavier , Hu Kai , Hiller Karl-Heinz , Boivin-Jahns Valerie , Jakob Peter M. , Jahns Roland , Bauer Wolfgang R. 
Published: September 2013

Background—
Monocytes and macrophages are indispensable in the healing process after myocardial infarction (MI); however, the spatiotemporal distribution of monocyte infiltration and its correlation to prognostic indicators of reperfused MI have not been well described.

Methods and Results—

With combined fluorine 19/proton (
1
H) magnetic resonance imaging, we noninvasively visualized the spatiotemporal recruitment of monocytes in vivo in a rat model of reperfused MI. Blood monocytes were labeled by intravenous injection of
19
F-perfluorocarbon emulsion 1 day after MI. The distribution patterns of monocyte infiltration were correlated to the presence of microvascular obstruction (MVO) and intramyocardial hemorrhage. In vivo,
19
F/
1
H magnetic resonance imaging performed in series revealed that monocyte infiltration was spatially inhomogeneous in reperfused MI areas. In the absence of MVO, monocyte infiltration was more intense in MI regions with serious ischemia-reperfusion injuries, indicated by severe intramyocardial hemorrhage; however, monocyte recruitment was significantly impaired in MVO areas accompanied by severe intramyocardial hemorrhage. Compared with MI with isolated intramyocardial hemorrhage, MI with MVO resulted in significantly worse pump function of the left ventricle 28 days after MI.

Conclusions—

Monocyte recruitment was inhomogeneous in reperfused MI tissue. It was highly reduced in MVO areas defined by magnetic resonance imaging. The impaired monocyte infiltration in MVO regions could be related to delayed healing and worse functional outcomes in the long term. Therefore, monocyte recruitment in MI with MVO could be a potential diagnostic and therapeutic target that could be monitored noninvasively and longitudinally by
19
F/
1
H magnetic resonance imaging in vivo.
Planktonic ostracods (Myodocopa: Halocyprididae) from abyssopelagic depths in the Atlantic, North Pacific and Gulf of Oman: Chavturia abyssopelagica (n. gen., n. sp.), alocypretta profunda (n. sp.), Halocypretta parvirostrata Chavtur and Stovbun, 2008 and Halocypretta striata (Müller, 1906)
Authors: ANGEL MARTIN V. 
Published: September 2013

A novel species and genus of halocyprid ostracod, Chavturia abyssopelagica, and a new species of Halocypretta are described from depths >3000 m in the Atlantic. The new genus is related to Halocypretta, itself a genus that has only recently been described from deep waters in the North Pacific. Supplementary observations are made on the type species, Halocypretta parvirostrata, based on additional specimens from the North Pacific. Halocypretta striata from the Gulf of Oman is reported for the first time since it was first described and is redescribed in detail. All four species are illustrated and compared using a set of meristic characters.