bluuebunny/crossref_metadata_2025_split huggingface dataset:
Skewed B cells in chronic hepatitis C virus infection maintain their ability to respond to virus‐induced activation
Authors: Oliviero B. , Mantovani S. , Ludovisi S. , Varchetta S. , Mele D. , Paolucci S. , Baldanti F. , Mondelli M. U. 
Published: September 2014

SummaryChronic hepatitis C virus (HCV) infection is characterized by persistent B‐cell activation, with enhanced differentiation and reduced proliferative ability. To assess the possible role of HCV in altering B‐cell subset distribution, we examined ex vivo frequencies and B‐cell inhibitory receptor expression in 37 chronic HCV‐infected patients and 25 healthy donors (HD). In addition, we determined whether short‐term exposure to culture‐derived HCV (HCVcc) resulted in B‐cell subset skewing and/or activation. There was a statistically significant increase in the frequencies of immature transitional, activated memory and tissue‐like memory (TLM) B cells in HCV‐infected patients compared with HD. We also found that the frequency of memory B cells correlated with serum HCV RNA levels. The proportion of B cells expressing the marker of exhaustion Fc receptor‐like 4 (FcRL4) was generally low even though significantly higher in the patients' memory B‐cell compartment compared with HD, and a positive correlation was found between the frequencies of the patients' TLM FcRL4+ B cells and serum alanine aminotransferase and histological activity index at liver biopsy. Exposure to cell‐free HCVcc in vitro did not result in B‐cell skewing but induced significant activation of naïve, TLM and resting memory B cells in HCV‐infected patients but not in HD, in whom cell‐associated virus was an absolute requirement for activation of memory B cells. These findings provide corroborative evidence in favour of significant B‐cell subset skewing in chronic HCV infection and in addition show that expression of exhaustion markers in selected B‐cell subsets does not impair virus‐induced B‐cell activation.
Contribution of glucan‐binding protein A to firm and stable biofilm formation by Streptococcus mutans
Authors: Matsumi Y. , Fujita K. , Takashima Y. , Yanagida K. , Morikawa Y. , Matsumoto‐Nakano M. 
Published: September 2014

SummaryGlucan‐binding proteins (Gbps) of Streptococcus mutans, a major pathogen of dental caries, mediate the binding of glucans synthesized from sucrose by the action of glucosyltransferases (GTFs) encoded by gtfB, gtfC, and gtfD. Several stress proteins, including DnaK and GroEL encoded by dnaK and groEL, are related to environmental stress tolerance. The contribution of Gbp expression to biofilm formation was analyzed by focusing on the expression levels of genes encoding GTFs and stress proteins. Biofilm‐forming assays were performed using GbpA‐, GbpB‐, and GbpC‐deficient mutant strains and the parental strain MT8148. The expression levels of gtfB, gtfC, gtfD, dnaK, and groEL were evaluated by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Furthermore, the structure of biofilms formed by these Gbp‐deficient mutant strains was observed using confocal laser scanning microscopy (CLSM). Biofilm‐forming assay findings demonstrated that the amount formed by the GbpA‐deficient mutant strain (AD1) was nearly the same as that by the parental strain, while the GbpB‐ and GbpC‐deficient mutant strains produced lower amounts than MT8148. Furthermore, RT‐qPCR assay results showed that the expressions of gtfB, dnaK, and groEL in AD1 were elevated compared with MT8148. CLSM also revealed that the structure of biofilm formed by AD1 was prominently different compared with that formed by the parental strain. These results suggest that a defect in GbpA influences the expression of genes controlling biofilm formation, indicating its importance as a protein for firm and stable biofilm formation.
Gestational Age‐Specific Associations between Infantile Acute Bronchiolitis and Asthma after Age Five
Authors: Strickland Matthew J. , Marsh Caitlin A. , Darrow Lyndsey A. 
Published: September 2014

AbstractBackgroundInfantile acute bronchiolitis (AB) is a risk factor for the development of paediatric asthma. The associations might differ according to gestational age.MethodsData sets of emergency department (ED) visits (January 2002 to June 2010) and livebirth records (January 2002 to December 2004) from the state of Georgia were linked for all children who survived 1 year. Exposure was an ED visit for AB during infancy, and the outcome was an ED visit for asthma after age 5 years. The risk of asthma among children with AB (n = 11 564) was compared with the risk of asthma among children who did not have an ED visit for AB but who utilised the ED for another reason during infancy (n = 131 694). Associations were estimated using log‐binomial regression models that controlled for several plausible confounders. Effect measure modification of the risk ratio by gestational age was investigated.ResultsUnadjusted asthma risks (per 100 children) through June 2010 were 4.5 for children with AB and 2.3 for children without AB. The adjusted risk ratio for the overall association was 1.9 [95% confidence interval 1.7, 2.1]. We did not observe effect modification of the risk ratio by gestational age.ConclusionA positive association was observed between ED visits for AB and subsequent asthma ED visits after age 5; associations did not vary meaningfully by gestational age. Sensitivity analyses did not suggest large biases due to differences in ED utilisation across sociodemographic groups or loss to follow‐up from residential migration.
Optimizing Electrical Activation of Porcine Oocytes by Adjusting Pre‐ and Post‐Activation Mannitol Exposure Times
Authors: Kwon D , Saadeldin IM , Kim SJ , Park SJ , Kang JT , Park HJ , Moon JH , Koo OJ , Jang G , Lee BC 
Published: September 2014

ContentsModifying electrical activation conditions have been used to improve in vitro embryo production and development in pigs. However, there is insufficient information about correlations of porcine embryo development with oocyte pre‐ and post‐activation conditions. The purpose of this study was to compare the developmental rates of porcine oocytes subjected to different mannitol exposure times, either pre‐ or post‐electrical activation, and to elucidate the reason for the optimal mannitol exposure time. Mannitol exposure times around activation were adjusted as 0, 1, 2 or 3 min. Blastocyst development were checked on day 7. Exposure of oocytes to mannitol for 1 or 2 min before electrical activation produced significantly higher blastocyst rates than exposure for 0 or 3 min. There was no significant difference in blastocyst rates when activated oocytes were exposed to mannitol for 0, 1, 2 or 3 min after electrical activation. While exposure of oocytes to mannitol for 1 min pre‐ and 3 min post‐activation showed significantly higher blastocyst development than 0 min pre‐ and 0 min post‐activation. It also showed higher maintenance of normal oocyte morphology than exposure for 0 min pre‐ and 0 min post‐activation. In conclusion, exposure of oocytes to mannitol for 1 min pre‐ and 3 min post‐activation seems to be optimal for producing higher in vitro blastocyst development of porcine parthenogenetic embryos. The higher blastocyst development is correlated with higher maintenance of normal morphology in oocytes exposed to mannitol for 1 min pre‐ and 3 min post‐activation.
Local Dependence in Random Graph Models: Characterization, Properties and Statistical Inference
Authors: Schweinberger Michael , Handcock Mark S. 
Published: September 2014

SummaryDependent phenomena, such as relational, spatial and temporal phenomena, tend to be characterized by local dependence in the sense that units which are close in a well-defined sense are dependent. In contrast with spatial and temporal phenomena, though, relational phenomena tend to lack a natural neighbourhood structure in the sense that it is unknown which units are close and thus dependent. Owing to the challenge of characterizing local dependence and constructing random graph models with local dependence, many conventional exponential family random graph models induce strong dependence and are not amenable to statistical inference. We take first steps to characterize local dependence in random graph models, inspired by the notion of finite neighbourhoods in spatial statistics and M-dependence in time series, and we show that local dependence endows random graph models with desirable properties which make them amenable to statistical inference. We show that random graph models with local dependence satisfy a natural domain consistency condition which every model should satisfy, but conventional exponential family random graph models do not satisfy. In addition, we establish a central limit theorem for random graph models with local dependence, which suggests that random graph models with local dependence are amenable to statistical inference. We discuss how random graph models with local dependence can be constructed by exploiting either observed or unobserved neighbourhood structure. In the absence of observed neighbourhood structure, we take a Bayesian view and express the uncertainty about the neighbourhood structure by specifying a prior on a set of suitable neighbourhood structures. We present simulation results and applications to two real world networks with ‘ground truth’.
Causal Inference from 2K Factorial Designs by Using Potential Outcomes
Authors: Dasgupta Tirthankar , Pillai Natesh S. , Rubin Donald B. 
Published: September 2014

SummaryA framework for causal inference from two-level factorial designs is proposed, which uses potential outcomes to define causal effects. The paper explores the effect of non-additivity of unit level treatment effects on Neyman's repeated sampling approach for estimation of causal effects and on Fisher's randomization tests on sharp null hypotheses in these designs. The framework allows for statistical inference from a finite population, permits definition and estimation of estimands other than ‘average factorial effects’ and leads to more flexible inference procedures than those based on ordinary least squares estimation from a linear model.
A report on the conservation status of segetal weeds in Tajikistan
Authors: Nowak A , Nowak S , Nobis M , Nobis A 
Published: September 2014

SummaryIntensification of agriculture has significantly diminished the populations of segetal weeds worldwide in recent decades. Remarkable changes to the entire flora and vegetation of man‐made habitats are being observed in agroecosystems. The present study analyses, for the first time, the threat status of segetal weeds in Tajikistan. A group of 871 weed species were evaluated against IUCN criteria. The assessment of threat status revealed that 214 weed taxa have to be regarded as threatened in Tajikistan, including 18 endemic and four subendemic plants. Five species have been classified as extinct, 27 as critically endangered, 27 as endangered, 39 as vulnerable, 34 as near threatened and 44 as in the ‘least concern’ category. For 38 species, the threat level was not possible, due to lack of data. The most threatened group of taxa is related to rice paddy fields. Numerous losses and disappearances were also observed in cereal communities. Percentages of threatened species in different chorological groups amounted to 58% in the Irano–Turanian, 17% in the Pluriregional, 11% in the Mediterranean, 9.5% in the Cosmopolitan and 4% in the Euro–Siberian species group. Assessment of the threatened status of the rich segetal flora of Tajikistan affords the opportunity to raise awareness of the value of this group of species in the country and may be useful in the conservation management of arable habitats. The results show that even though agriculture in Tajikistan is still based on traditional management and manual work, weed control causes a serious threat to its segetal flora.
Characterization and Protective Property of Brucella abortuscydCandlooPMutants
Authors: Truong Quang Lam , Cho Youngjae , Barate Abhijit Kashinath , Kim Suk , Hahn Tae-Wook 
Published: September 2014

ABSTRACTBrucella abortusreadily multiplies in professional or nonprofessional phagocytesin vitroand is highly virulent in mice. Isogenic mutants ofB. abortusbiovar 1 strain IVKB9007 lacking the ATP/GDP-binding protein motif A (P-loop) (namedlooP; designated here the IVKB9007looP::Tn5mutant) and the ATP-binding/permease protein (cydC; designated here the IVKB9007cydC::Tn5mutant) were identified and characterized by transposon mutagenesis using the mini-Tn5Km2 transposon. Both mutants were found to be virtually incapable of intracellular replication in both murine macrophages (RAW264.7) and the HeLa cell line, and their virulence was significantly impaired in BALB/c mice. Respective complementation of the IVKB9007looP::Tn5and IVKB9007cydC::Tn5mutants restored their ability to survivein vitroandin vivoto a level comparable with that of the wild type. These findings indicate that thecydCandlooPgenes play important roles in the virulence ofB. abortus. In addition, intraperitoneal immunization of mice with a dose of the live IVKB9007looP::Tn5and IVKB9007cydC::Tn5mutants provided a high degree of protection against challenge with pathogenicB. abortusstrain 544. Both mutants should be evaluated further as a live attenuated vaccine against bovine brucellosis for their ability to stimulate a protective immune response.
Inter- and Intralaboratory Comparison of JC Polyomavirus Antibody Testing Using Two Different Virus-Like Particle-Based Assays
Authors: Kardas Piotr , Sadeghi Mohammadreza , Weissbach Fabian H. , Chen Tingting , Hedman Lea , Auvinen Eeva , Hedman Klaus , Hirsch Hans H. 
Published: September 2014

ABSTRACT

JC polyomavirus (JCPyV) can cause progressive multifocal leukoencephalopathy (PML), a debilitating, often fatal brain disease in immunocompromised patients. JCPyV-seropositive multiple sclerosis (MS) patients treated with natalizumab have a 2- to 10-fold increased risk of developing PML. Therefore, JCPyV serology has been recommended for PML risk stratification. However, different antibody tests may not be equivalent. To study intra- and interlaboratory variability, sera from 398 healthy blood donors were compared in 4 independent enzyme-linked immunoassay (ELISA) measurements generating >1,592 data points. Three data sets (Basel1, Basel2, and Basel3) used the same basic protocol but different JCPyV virus-like particle (VLP) preparations and introduced normalization to a reference serum. The data sets were also compared with an independent method using biotinylated VLPs (Helsinki1). VLP preadsorption reducing ≥35% activity was used to identify seropositive sera. The results indicated that Basel1, Basel2, Basel3, and Helsinki1 were similar regarding overall data distribution (
P
= 0.79) and seroprevalence (58.0, 54.5, 54.8, and 53.5%, respectively;
P
= 0.95). However, intra-assay intralaboratory comparison yielded 3.7% to 12% discordant results, most of which were close to the cutoff (0.080 < optical density [OD] < 0.250) according to Bland-Altman analysis. Introduction of normalization improved overall performance and reduced discordance. The interlaboratory interassay comparison between Basel3 and Helsinki1 revealed only 15 discordant results, 14 (93%) of which were close to the cutoff. Preadsorption identified specificities of 99.44% and 97.78% and sensitivities of 99.54% and 95.87% for Basel3 and Helsinki1, respectively. Thus, normalization to a preferably WHO-approved reference serum, duplicate testing, and preadsorption for samples around the cutoff may be necessary for reliable JCPyV serology and PML risk stratification.
Maintenance of Leptospira Species in Leptospira Vanaporn Wuthiekanun Agar
Authors: Wuthiekanun Vanaporn , Amornchai Premjit , Langla Sayan , Oyuchua Malinee , Day Nicholas P. J. , Limmathurotsakul Direk 
Published: September 2014

ABSTRACT

The maintenance of
Leptospira
species in liquid or semisolid medium is time-consuming and at risk of contamination due to the needs of routine subculture and dark field microscopy. Using
Leptospira
Vanaporn Wuthiekanun (LVW) agar, we maintained 100 pathogenic
Leptospira
isolates for 12 months without the need for subculture and confirmed the viability of all isolates by the naked eye.
Evaluation of the Xpert Flu Rapid PCR Assay in High-Risk Emergency Department Patients
Authors: Dugas Andrea F. , Valsamakis Alexandra , Gaydos Charlotte A. , Forman Michael , Hardick Justin , Kidambi Pranav , Amin Sharmeen , Gupta Alisha , Rothman Richard E. 
Published: September 2014

ABSTRACT
We prospectively evaluated the performance of Cepheid's GeneXpert Xpert Flu assay in a target population of 281 adults presenting to the emergency department with an acute respiratory illness who met Centers for Disease Control and Prevention (CDC) criteria for recommended antiviral treatment. Compared with the Prodesse ProFlu+ assay, Xpert Flu had an overall sensitivity of 95.3% and specificity of 99.2%.
Point-Counterpoint: Consolidated Clinical Microbiology Laboratories
Authors: Sautter Robert L. , Thomson Richard B. 
Published: September 2014

ABSTRACT
The manner in which medical care is reimbursed in the United States has resulted in significant consolidation in the U.S. health care system. One of the consequences of this has been the development of centralized clinical microbiology laboratories that provide services to patients receiving care in multiple off-site, often remote, locations. Microbiology specimens are unique among clinical specimens in that optimal analysis may require the maintenance of viable organisms. Centralized laboratories may be located hours from patient care settings, and transport conditions need to be such that organism viability can be maintained under a variety of transport conditions. Further, since the provision of rapid results has been shown to enhance patient care, effective and timely means for generating and then reporting the results of clinical microbiology analyses must be in place. In addition, today, increasing numbers of patients are found to have infection caused by pathogens that were either very uncommon in the past or even completely unrecognized. As a result, infectious disease specialists, in particular, are more dependent than ever on access to high-quality diagnostic information from clinical microbiology laboratories. In this point-counterpoint discussion, Robert Sautter, who directs a Charlotte, NC, clinical microbiology laboratory that provides services for a 40-hospital system spread over 3 states in the southeastern United States explains how an integrated clinical microbiology laboratory service has been established in a multihospital system. Richard (Tom) Thomson of the NorthShore University HealthSystem in Evanston, IL, discusses some of the problems and pitfalls associated with large-scale laboratory consolidation.
Quantitation of Replication-Competent HIV-1 in Populations of Resting CD4
+
T Cells
Authors: Soriano-Sarabia Natalia , Bateson Rosalie E. , Dahl Noelle P. , Crooks Amanda M. , Kuruc JoAnn D. , Margolis David M. , Archin Nancie M. 
Published: September 2014

ABSTRACT

Central memory (T
CM
) CD4
+
T cells are the principal reservoir of latent HIV-1 infection that persists despite durable, successful antiretroviral therapy (ART). In a study that measured HIV DNA in 17 patients and replication-competent HIV in 4 patients, pools of resting and activated transitional memory (T
TM
) CD4
+
T cells were found to be a reservoir for HIV infection. As defective viruses account for the majority of integrated HIV DNA and do not reflect the actual frequency of latent, replication-competent proviral infection, we assessed the specific contribution of resting T
TM
cells to latent HIV infection. We measured the frequency of replication-competent HIV in purified resting memory cell subpopulations by a limiting-dilution, quantitative viral outgrowth assay (QVOA). HIV was routinely detected within the resting central memory compartment but was infrequently detected within the resting T
TM
compartment. These observations suggest that prolonged ART may limit persistent latent infection in the T
TM
compartment. Our results confirm the importance of latent infection within the T
CM
compartment and again focus attention on these cells as the most important latent viral reservoir. While proliferation may drive expansion of detectable viral genomes in cells, the frequency of replication-competent HIV must be carefully assessed. Latent infection appears to wane within the transitional memory compartment in patients who have sustained successful viral suppression via ART or were treated very early in infection.

IMPORTANCE
Antiretroviral therapy (ART) has led to a significant decrease in morbidity and mortality among HIV-infected patients. However, HIV integrates into the genome of CD4
+
T cells, generating pools of long-lived cells that are reservoirs of latent HIV. Two main subsets of CD4
+
T cells, central memory and transitional memory cells, were reported to be major reservoirs of HIV infection. However, this study primarily measured the HIV DNA content, which also includes defective proviruses that would not be able to replicate and initiate new rounds of infection. By analyzing the replication-competent virus in both cell subsets, we showed that transitional memory cells may not be a durable reservoir in patients on successful ART.
Hijacking Dlg1 for Oncogenic Phosphatidylinositol 3-Kinase Activation in Human Epithelial Cells Is a Conserved Mechanism of Human Adenovirus E4-ORF1 Proteins
Authors: Kumar Manish , Kong Kathleen , Javier Ronald T. 
Published: September 2014

ABSTRACT

The
E4-ORF1
gene of human adenoviruses encodes a 14-kDa protein that promotes viral replication as well as cellular metabolic reprogramming, survival, and transformation by constitutively activating cellular phosphatidylinositol 3-kinase (PI3K). We recently reported that the E4-ORF1 protein from subgroup D human adenovirus type 9 upregulates and oncogenically activates PI3K by a novel mechanism involving separate interactions of E4-ORF1 with cellular discs large 1 (Dlg1) and PI3K to form a ternary complex that translocates to the plasma membrane (K. Kong, M. Kumar, M. Taruishi, and R. T. Javier, PLoS Pathog. 10:e1004102, 2014, doi:10.1371/journal.ppat.1004102). The current study was carried out to investigate whether other human adenovirus E4-ORF1 proteins share this mechanism of action. The results showed that in human MCF10A epithelial cells, stable expression of E4-ORF1 proteins encoded by representative human adenovirus serotypes from subgroups A to D induce ternary complex formation, Dlg1-dependent PI3K activation, PI3K protein elevation, Dlg1 and PI3K membrane recruitment, and PI3K-dependent cellular transformation. The first three of these E4-ORF1 activities were also observed in MCF10A cells infected with each wild-type human adenovirus from subgroups A to D. Our findings indicate that most, if not all, human adenovirus E4-ORF1 proteins share a conserved molecular mechanism of PI3K activation, which confers a common capacity to promote oncogenic transformation in human epithelial cells.

IMPORTANCE
PI3K activation by the adenovirus E4-ORF1 protein mediates oncogenic cellular transformation by human adenovirus type 9, augments viral protein expression and replication by human adenovirus type 5, and dysregulates cellular glucose and lipid metabolism by human adenovirus type 36. For the first time, we report that E4-ORF1 proteins from human adenoviruses in subgroups A to D evolved a conserved molecular mechanism to mediate constitutive PI3K activation that can provoke oncogenic transformation in human epithelial cells. The results raise potential safety concerns about the use of vectors encoding the
E4-ORF1
gene in human gene therapy and vaccination. Our findings further suggest that the conserved mechanism revealed here may be targeted for development of therapeutic drugs to treat and prevent adenovirus-associated human diseases.