bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver type I regulatory T cells suppress germinal center formation in HBV-tolerant mice
Authors: Xu Long , Yin Wenwei , Sun Rui , Wei Haiming , Tian Zhigang 
Published: October 2013

Significance
We present a unique study of a liver-induced systemic tolerance using an intact virus, other than a single protein component-induced liver-persistent model. Liver-educated regulatory cells migrate into peripheral sites and mediate the systemic tolerance. Kupffer cells induce the generation of type 1-like regulatory cells in an IL-10–dependent manner. A possible role of type 1-like regulatory cells in suppressing germinal center formation via secreting IL-10 is demonstrated. We observed that a “regulatory cell-based” tolerizing mechanism, rather than a “clonal deletion” mechanism, provides the possibility of reversing the tolerance by immunotherapeutic approaches.
Positional information, in bits
Authors: Dubuis Julien O. , Tkačik Gašper , Wieschaus Eric F. , Gregor Thomas , Bialek William 
Published: October 2013

Significance
In a developing embryo, individual cells need to “know” where they are to do the right thing. How much do they know, and where is this knowledge written down? Here, we show that these questions can be made mathematically precise. In the fruit fly embryo, information about position is thought to be encoded by the concentration of particular protein molecules, and we measure this information, in bits. Just four different kinds of molecules are almost enough to specify the identity of every cell along the long axis of the embryo, and we argue that the way in which this information is distributed reflects an optimization principle, maximizing the information available from a limited number of molecules.
Salivary Biomarkers: Toward Future Clinical and Diagnostic Utilities
Authors: Yoshizawa Janice M. , Schafer Christopher A. , Schafer Jason J. , Farrell James J. , Paster Bruce J. , Wong David T. W. 
Published: October 2013

SUMMARYThe pursuit of timely, cost-effective, accurate, and noninvasive diagnostic methodologies is an endeavor of urgency among clinicians and scientists alike. Detecting pathologies at their earliest stages can significantly affect patient discomfort, prognosis, therapeutic intervention, survival rates, and recurrence. Diagnosis and monitoring often require painful invasive procedures such as biopsies and repeated blood draws, adding undue stress to an already unpleasant experience. The discovery of saliva-based microbial, immunologic, and molecular biomarkers offers unique opportunities to bypass these measures by utilizing oral fluids to evaluate the condition of both healthy and diseased individuals. Here we discuss saliva and its significance as a source of indicators for local, systemic, and infectious disorders. We highlight contemporary innovations and explore recent discoveries that deem saliva a mediator of the body's physiological condition. Additionally, we examine the current state of salivary diagnostics and its associated technologies, future aspirations, and potential as the preferred route of disease detection, monitoring, and prognosis.
Recent Advances in Understanding Enteric Pathogenic Escherichia coli
Authors: Croxen Matthew A. , Law Robyn J. , Scholz Roland , Keeney Kristie M. , Wlodarska Marta , Finlay B. Brett 
Published: October 2013

SUMMARY

Although
Escherichia coli
can be an innocuous resident of the gastrointestinal tract, it also has the pathogenic capacity to cause significant diarrheal and extraintestinal diseases. Pathogenic variants of
E. coli
(pathovars or pathotypes) cause much morbidity and mortality worldwide. Consequently, pathogenic
E. coli
is widely studied in humans, animals, food, and the environment. While there are many common features that these pathotypes employ to colonize the intestinal mucosa and cause disease, the course, onset, and complications vary significantly. Outbreaks are common in developed and developing countries, and they sometimes have fatal consequences. Many of these pathotypes are a major public health concern as they have low infectious doses and are transmitted through ubiquitous mediums, including food and water. The seriousness of pathogenic
E. coli
is exemplified by dedicated national and international surveillance programs that monitor and track outbreaks; unfortunately, this surveillance is often lacking in developing countries. While not all pathotypes carry the same public health profile, they all carry an enormous potential to cause disease and continue to present challenges to human health. This comprehensive review highlights recent advances in our understanding of the intestinal pathotypes of
E. coli
.
Update on Tick-Borne Rickettsioses around the World: a Geographic Approach
Authors: Parola Philippe , Paddock Christopher D. , Socolovschi Cristina , Labruna Marcelo B. , Mediannikov Oleg , Kernif Tahar , Abdad Mohammad Yazid , Stenos John , Bitam Idir , Fournier Pierre-Edouard , Raoult Didier 
Published: October 2013

SUMMARYTick-borne rickettsioses are caused by obligate intracellular bacteria belonging to the spotted fever group of the genusRickettsia. These zoonoses are among the oldest known vector-borne diseases. However, in the past 25 years, the scope and importance of the recognized tick-associated rickettsial pathogens have increased dramatically, making this complex of diseases an ideal paradigm for the understanding of emerging and reemerging infections. Several species of tick-borne rickettsiae that were considered nonpathogenic for decades are now associated with human infections, and novelRickettsiaspecies of undetermined pathogenicity continue to be detected in or isolated from ticks around the world. This remarkable expansion of information has been driven largely by the use of molecular techniques that have facilitated the identification of novel and previously recognized rickettsiae in ticks. New approaches, such as swabbing of eschars to obtain material to be tested by PCR, have emerged in recent years and have played a role in describing emerging tick-borne rickettsioses. Here, we present the current knowledge on tick-borne rickettsiae and rickettsioses using a geographic approach toward the epidemiology of these diseases.
Pathogenesis and Current Approaches to Control of Varicella-Zoster Virus Infections
Authors: Gershon Anne A. , Gershon Michael D. 
Published: October 2013

SUMMARYVaricella-zoster virus (VZV) was once thought to be a fairly innocuous pathogen. That view is no longer tenable. The morbidity and mortality due to the primary and secondary diseases that VZV causes, varicella and herpes zoster (HZ), are significant. Fortunately, modern advances, including an available vaccine to prevent varicella, a therapeutic vaccine to diminish the incidence and ameliorate sequelae of HZ, effective antiviral drugs, a better understanding of VZV pathogenesis, and advances in diagnostic virology have made it possible to control VZV in the United States. Occult forms of VZV-induced disease have been recognized, including zoster sine herpete and enteric zoster, which have expanded the field. Future progress should include development of more effective vaccines to prevent HZ and a more complete understanding of the consequences of VZV latency in the enteric nervous system.
An Atypical Clostridium Strain Related to the Clostridium botulinum Group III Strain Isolated from a Human Blood Culture
Authors: Bouvet Philippe , Ruimy Raymond , Bouchier Christiane , Faucher Nathalie , Mazuet Christelle , Popoff Michel R. 
Published: October 2013

ABSTRACT

A nontoxigenic strain isolated from a fatal human case of bacterial sepsis was identified as a
Clostridium
strain from
Clostridium botulinum
group III, based on the phenotypic characters and 16S rRNA gene sequence, and was found to be related to the mosaic
C. botulinum
D/C strain according to a multilocus sequence analysis of 5 housekeeping genes.
Validation of the Gen-Probe Aptima Qualitative HIV-1 RNA Assay for Diagnosis of Human Immunodeficiency Virus Infection in Infants
Authors: Fiscus Susan A. , McMillion Takesha , Nelson Julie A. E. , Miller William C. 
Published: October 2013

ABSTRACT
The qualitative Roche HIV-1 DNA Amplicor assay has been used for the past 20 years to diagnose HIV infection in infants and young children but is being phased out; hence, alternative assays must be found. The Gen-Probe Aptima qualitative HIV-1 RNA assay is currently the only FDA-cleared HIV-1 nucleic acid assay approved for diagnosis, but data on the use of this assay with infant plasma are limited. We assessed Aptima's performance using control material for reproducibility and limit of detection and 394 plasma samples (0.2 to 0.5 ml) from HIV-exposed infected and uninfected infants and children for analytical sensitivity and specificity. Assays to assess within-run repeatability and between-run reproducibility indicated that the controls with 10,000 (5 of 5), 200 (5 of 5), 100 (16 of 16), 50 (12 of 12), and 25 (20 of 20) HIV-1 RNA copies/ml (cp/ml) were always positive, and negatives were always negative (20 of 20). The limit of detection was 14 cp/ml, as determined by probit analysis. The analytic sensitivity of the assay was 99.5% (189/190 samples; 95% confidence interval [CI], 97.1 to 99.9%) and specificity was 99.5% (199/200 samples; 95% CI, 97.2 to 99.9%). These results suggest that the assay is suitable for early infant diagnosis of HIV-1.
Impact of the New Abbott
m
PLUS Feature on Clinical Laboratory Efficiencies of Abbott RealTi
m
e Assays for Detection of HIV-1, Hepatitis C Virus, Hepatitis B Virus, Chlamydia trachomatis, and Neisseria gonorrhoeae
Authors: Lucic Danijela , Jones Sara , Wiesneth Russ , Barry Cathy , Webb Erika , Belova Larissa , Dolan Peggy , Ho Shiaolan , Abravaya Klara , Cloherty Gavin 
Published: October 2013

ABSTRACT

Diagnostic laboratories are under increasing pressure to improve and expand their services. Greater flexibility in sample processing is a critical factor that can improve the time to results while reducing reagent waste, making laboratories more efficient and cost-effective. The introduction of the Abbott
m
PLUS feature, with the capacity for extended use of amplification reagents, significantly increases the flexibility of the
m
2000 platform and enables laboratories to customize their workflows based on sample arrival patterns. The flexibility in sample batch size offered by
m
PLUS enables significant reductions in processing times. For hepatitis B virus tests, a reduction in sample turnaround times of up to 30% (105 min) was observed for batches of 12 samples compared with those for batches of 24 samples; for
Chlamydia trachomatis
/
Neisseria gonorrhoeae
tests, the ability to run batches of 24 samples reduced the turnaround time by 83% (54 min) compared with that for batches of 48 samples. Excellent correlations between
m
PLUS and
m
2000 standard condition results were observed for all RealTi
m
e viral load assays evaluated in this study, with correlation
r
values of 0.998 for all assays tested. For the qualitative RealTi
m
e
C. trachomatis
/
N. gonorrhoeae
assay, the overall agreements between the two conditions tested were >98% for
C. trachomatis
and 100% for
N. gonorrhoeae
. Comparable precision results were observed for the two conditions tested for all RealTi
m
e assays. The enhanced
m
PLUS capability provides clinical laboratories with increased efficiencies to meet increasingly stringent turnaround time requirements without increased costs associated with discarding partially used amplification reagents.
Comparison of Next-Generation Sequencing and Clone-Based Sequencing in Analysis of Hepatitis B Virus Reverse Transcriptase Quasispecies Heterogeneity
Authors: Gong Ling , Han Yue , Chen Li , Liu Feng , Hao Pei , Sheng Jia , Li Xin-Hua , Yu De-Min , Gong Qi-Ming , Tian Fei , Guo Xiao-kui , Zhang Xin-Xin 
Published: October 2013

ABSTRACT

We previously reported that, based on clone-based sequencing (CBS), hepatitis B virus (HBV) heterogeneity within the reverse transcriptase (RT) region was a predictor of antiviral efficacy. Here, by comparing ultradeep pyrosequencing (UDPS), i.e., next-generation sequencing (NGS), with CBS in characterizing the genetic heterogeneity of HBV quasispecies within the RT region, we evaluated the performance of UDPS in the analysis of HBV viral populations. HBV genomic DNA was extracted from serum samples from 31 antiviral treatment-naive patients with chronic hepatitis B. The RT region quasispecies were analyzed in parallel using CBS and UDPS. Characterization of quasispecies heterogeneity was conducted using bioinformatics analysis. Quasispecies complexity values were calculated with the formula
Sn
= −Σ

i

(

p
i

ln

p
i

)/ln
N
. The number of qualified strains obtained by UDPS was much larger than that obtained by CBS (
P
< 0.001). Pearson analysis showed that there was a positive correlation of quasispecies complexity values at the nucleotide level for the two methods (
P
< 0.05), while the complexity value derived from UDPS data was higher than that derived from CBS data (
P
< 0.001). Study of the prevalences of variations within the RT region showed that CBS detected an average of 9.7 ± 1.1 amino acid substitutions/sample and UDPS detected an average of 16.2 ± 1.4 amino acid substitutions/sample. The phylogenetic analysis based on UDPS data showed more genetic entities than did that based on CBS data. Viral heterogeneity determination by the UDPS technique is more sensitive and efficient in terms of low-abundance variation detection and quasispecies simulation than that by the CBS method, although imperfect, and thus sheds light on the future clinical application of NGS in HBV quasispecies studies.
Presence of Cross-Reactions with Other Viral Encephalitides in the Indirect Fluorescent-Antibody Test for Diagnosis of Rabies
Authors: Rudd Robert J. , Appler Kim A. , Wong Susan J. 
Published: October 2013

ABSTRACT

The antemortem diagnosis of rabies in humans employs techniques that require accuracy, speed, and sensitivity. A combination of histochemical analysis,
in vitro
virus isolation, immunological methods, and molecular amplification procedures are utilized in efforts to diagnose the disease. Modern medicine now offers potentially life-saving treatment for a disease that was considered invariably fatal once clinical signs develop. However, medical intervention efforts require a rapid and accurate diagnosis as early in the course of clinical disease as possible. Indirect fluorescent-antibody (IFA) testing on cerebrospinal fluid and serum specimens provides rapid results, but the specificity of the assay has not been well studied. Because false-positive IFA results could significantly affect patient treatment and outcomes, it is critical to understand the specificity of this assay. In this study, IFA testing was performed on 135 cerebrospinal fluid and serum specimens taken from patients with viral encephalitis or a presumed viral infection involving an agent other than rabies virus. Results indicate that false-positive results can occur in interpreting the rabies IFA test. Staining patterns morphologically similar to antirabies staining were observed in 7 of the 135 cerebrospinal fluid specimens examined. In addition, a majority of the cerebrospinal fluid specimens tested from patients with encephalitis presented immunoglobulin that bound to antigens present in the cell culture substrate. Of marked concern was the frequent presence of cross-reactive antibodies in encephalitis cases associated with West Nile and Powassan flaviviruses. Because IFA testing for rabies on human specimens may result in false-positive results, it should not be used as the sole basis for initiating antirabies treatment.
Marseillevirus Adenitis in an 11-Month-Old Child
Authors: Popgeorgiev Nikolay , Michel Gerard , Lepidi Hubert , Raoult Didier , Desnues Christelle 
Published: October 2013

ABSTRACT

A Marseillevirus (giant virus of amoeba) has been found in the blood and stool samples of individuals who otherwise appear to be healthy. During an attempt to define a serological cutoff for Marseillevirus by enzyme-linked immunosorbent assay (ELISA) in children, we serendipitously detected high antibody responses to Marseillevirus in an 11-month-old boy suffering from adenitis. Marseillevirus DNA was then found in his blood using PCR and with a unique sequence. We identified Marseillevirus in a lymph node using fluorescence
in situ
hybridization (FISH) and immunohistochemistry, and the lymph node was removed surgically. The child was declared to be cured 1 year later. We conclude that adenitis during early childhood may be caused by Marseillevirus.
wzi
Gene Sequencing, a Rapid Method for Determination of Capsular Type for Klebsiella Strains
Authors: Brisse Sylvain , Passet Virginie , Haugaard Anita Björk , Babosan Anamaria , Kassis-Chikhani Najiby , Struve Carsten , Decré Dominique 
Published: October 2013

ABSTRACT

Pathogens of the genus
Klebsiella
have been classified into distinct capsular (K) types for nearly a century. K typing of
Klebsiella
species still has important applications in epidemiology and clinical microbiology, but the serological method has strong practical limitations. Our objective was to evaluate the sequencing of
wzi
, a gene conserved in all capsular types of
Klebsiella pneumoniae
that codes for an outer membrane protein involved in capsule attachment to the cell surface, as a simple and rapid method for the prediction of K type. The sequencing of a 447-nucleotide region of
wzi
distinguished the K-type reference strains with only nine exceptions. A reference
wzi
sequence database was created by the inclusion of multiple strains representing K types associated with high virulence and multidrug resistance. A collection of 119 prospective clinical isolates of
K. pneumoniae
were then analyzed in parallel by
wzi
sequencing and classical K typing. Whereas K typing achieved typeability for 81% and discrimination for 94.4% of the isolates, these figures were 98.1% and 98.3%, respectively, for
wzi
sequencing. The prediction of K type once the
wzi
allele was known was 94%.
wzi
sequencing is a rapid and simple method for the determination of the K types of most
K. pneumoniae
clinical isolates.
Large Oligoclonal Outbreak Due to Klebsiella pneumoniae ST14 and ST26 Producing the FOX-7 AmpC β-Lactamase in a Neonatal Intensive Care Unit
Authors: Arena Fabio , Giani Tommaso , Becucci Elisa , Conte Viola , Zanelli Giacomo , D'Andrea Marco Maria , Buonocore Giuseppe , Bagnoli Franco , Zanchi Alessandra , Montagnani Francesca , Rossolini Gian Maria 
Published: October 2013

ABSTRACT

A large outbreak caused by expanded-spectrum cephalosporin-resistant
Klebsiella pneumoniae
(ESCRKP) was observed in a neonatal intensive care unit (NICU) in central Italy. The outbreak involved 127 neonates (99 colonizations and 28 infections, with seven cases of sepsis and two deaths) over a period of more than 2 years (February 2008 to April 2010). Characterization of the 92 nonredundant isolates that were available for further investigation revealed that all of them except one produced the FOX-7 AmpC-type β-lactamase and belonged to either sequence type 14 (ST14) or ST26. All of the FOX-7-positive isolates were resistant to cefotaxime, ceftazidime, and piperacillin-tazobactam, while 76% were susceptible to cefepime, 98% to ertapenem, 99% to meropenem, and 100% to imipenem. The two carbapenem-nonsusceptible isolates had alterations in the genes encoding outer membrane proteins K35 and K36, which resulted in truncated and likely nonfunctional proteins. The outbreak was eventually controlled by the reinforcement of infection control measures based on a multitiered interventional approach. This is the first report of a large NICU outbreak caused by ESCRKP producing an AmpC-type enzyme. This study demonstrates that AmpC-type enzyme-producing strains can cause large outbreaks with significant morbidity and mortality effects (the mortality rate at 14 days was 28.5% for episodes of sepsis), and it underscores the role of laboratory-based surveillance and infection control measures to contain similar episodes.
Clinical Prediction and Diagnosis of Neurosyphilis in HIV-Infected Patients with Early Syphilis
Authors: Dumaresq Jeannot , Langevin Stéphanie , Gagnon Simon , Serhir Bouchra , Deligne Benoît , Tremblay Cécile , Tsang Raymond S. W. , Fortin Claude , Coutlée François , Roger Michel 
Published: October 2013

ABSTRACT

The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected patients, and the criteria for deciding when to perform a lumbar puncture (LP) in HIV-infected patients with syphilis are controversial. We retrospectively reviewed demographic, clinical, and laboratory data from 122 cases of HIV-infected patients with documented early syphilis who underwent an LP to rule out NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the
Treponema pallidum
particle agglutination (TPPA) assay, the fluorescent treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white blood cell (WBC) count of >20 cells/μl. Thirty of the 122 patients (24.6%) had early NS. Headache, visual symptoms, a CD4 cell count of <500 cells/μl, and viremia, as defined by an HIV-1 RNA count of ≥50 copies/ml, were associated with NS in multivariate analysis (
P
= <0.001 for each factor). Blood serum rapid plasma reagin (RPR) titers were not associated with early NS (
P
= 0.575). For the diagnosis of NS, the PCR, FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of 58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances, headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/μl were predictors of NS in HIV-infected patients with early syphilis, while blood serum RPR titers were not; therefore, RPR titers should not be used as the sole criterion for deciding whether to perform an LP in early syphilis. When applied to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS.
The μ1 72-96 Loop Controls Conformational Transitions during Reovirus Cell Entry
Authors: Sarkar Payel , Danthi Pranav 
Published: October 2013

ABSTRACT
The reovirus outer capsid protein μ1 forms a lattice surrounding the viral core. In the native state, μ1 determines the environmental stability of the viral capsid. Additionally, during cell entry, μ1 undergoes structural rearrangements that facilitate delivery of the viral cores across the membrane. To determine how the capsid-stabilizing functions of μ1 impinge on the capacity of μ1 to undergo conformational changes required for cell entry, we characterized viruses with mutations engineered at charged residues within the μ1 loop formed by residues 72 to 96 (72-96 loop). This loop is proposed to stabilize the capsid by mediating interactions between neighboring μ1 trimers and between trimers and the core. We found that mutations at Glu89 (E89) within this loop produced viruses with compromised efficiency for completing their replication cycle. ISVPs of E89 mutants converted to ISVP*s more readily than those of wild-type viruses. The E89 mutants yielded revertants with second-site substitutions within regions that mediate interaction between μ1 trimers at a site distinct from the 72-96 loop. These viruses also contained changes in regions that control interactions within μ1 trimers. Viruses containing these second-site changes displayed restored plaque phenotypes and were capable of undergoing ISVP-to-ISVP* conversion in a regulated manner. These findings highlight regions of μ1 that stabilize the reovirus capsid and demonstrate that an enhanced propensity to form ISVP*s in an unregulated manner compromises viral fitness.