bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeated Cortico-Striatal Stimulation Generates Persistent OCD-Like Behavior
Authors: Ahmari Susanne E. , Spellman Timothy , Douglass Neria L. , Kheirbek Mazen A. , Simpson H. Blair , Deisseroth Karl , Gordon Joshua A. , Hen René
Published: June 2013

What Causes Obsessive Compulsive Disorder?

Obsessive compulsive disorder is a severe, chronic mental illness that affects millions of individuals. However, the mechanisms underlying this disease are still largely unknown (see the Perspective by

Rauch and Carlezon Jr.

).

Ahmari
et al.

(p.
1234
) stimulated glutamatergic pathways between the orbitofrontal cortex and the ventromedial striatum and used grooming to assess obsessive compulsive behavior in mice. Repetitive stimulation over days triggered changes in the neuronal responses of the ventromedial striatum. Over time, the behavior of the animals became independent of stimulation and could be prevented by the antidepressant fluoxetine.

Burguière
et al.

(p.
1243
) investigated the neural basis of obsessive compulsive symptoms in a mutant mouse that showed excessive expression of a conditioned form of grooming.
Growing Self-Organizing Mini-Guts from a Single Intestinal Stem Cell: Mechanism and Applications
Authors: Sato Toshiro , Clevers Hans
Published: June 2013

Recent examples have highlighted how stem cells have the capability to initiate morphogenesis in vitro; that is, to generate complex structures in culture that closely parallel their in vivo counterparts. Lgr5, the receptor for the Wnt-agonistic R-spondins, marks stem cells in multiple adult organs of mice and humans. In R-spondin–based three-dimensional cultures, these Lgr5 stem cells can grow into ever-expanding epithelial organoids that retain their original organ identity. Single Lgr5 stem cells derived from the intestine can be cultured to build epithelial structures that retain hallmarks of the in vivo epithelium. Here, we review the mechanisms that support this notable example of self-organization and discuss applications of this technology for stem cell research, disease modeling (e.g., for colorectal cancer and cystic fibrosis), and regenerative medicine.
Probing the Solar Magnetic Field with a Sun-Grazing Comet
Authors: Downs Cooper , Linker Jon A. , Mikić Zoran , Riley Pete , Schrijver Carolus J. , Saint-Hilaire Pascal
Published: June 2013

A Comet in the Sun

In 2011, comet Lovejoy plunged into the solar atmosphere and survived its flight through a region of the Sun that has never been visited by spacecraft.

Downs
et al.

(p.
1196
) used spacecraft observations of this Sun-grazing comet, combined with advanced magnetohydrodynamic simulations, to constrain the magnetic field of the solar atmosphere—a quantity that has been very difficult to measure directly.
What Led to Metazoa's Big Bang?
The Cambrian Explosion
The Construction of Animal Biodiversity

by Douglas H. Erwin and James W. Valentine

Roberts and Company, Greenwood Village, CO, 2013. 416 pp., illus. $60. ISBN 9781936221035.
Authors: Lowe Christopher J.
Published: June 2013

Erwin and Valentine explore the roles that changes in the physical environment, ecological relationships, and developmental systems—as well as interactions among the three elements—played in the Cambrian explosion.
Illuminating the Neural Circuitry of Compulsive Behaviors
Authors: Rauch Scott L. , Carlezon William A.
Published: June 2013

Optogenetics is used to delineate and control a brain circuit that drives repetitive behavior in an animal model, opening up new possibilities for the treatment of compulsive disorders.

[Also see Reports by

Ahmari
et al.

and

Burguière
et al.

]
Authenticity of China's Fabulous Fossils Gets New Scrutiny
Authors: Balter Michael
Published: June 2013

Northeastern China has produced amazingly detailed fossils of feathered dinosaurs and early birds, but sloppy record-keeping and outright forgeries make it hard for paleontologists to tell where many secondhand specimens came from, how old they are, and whether they are authentic.
Comparison of the Vidas System and Two Recent Fully Automated Assays for Diagnosis and Follow-Up of Toxoplasmosis in Pregnant Women and Newborns
Authors: Murat Jean-Benjamin , Dard Céline , Fricker Hidalgo Hélène , Dardé Marie-Laure , Brenier-Pinchart Marie-Pierre , Pelloux Hervé
Published: June 2013

Serological testing to detect toxoplasmosis is of major importance to avoid the possible effects of the disease in newborns. This study assessed anti-
Toxoplasma
IgG and IgM with the Vidas (bioMérieux), Architect (Abbott), and Liaison (DiaSorin) systems in 631 sera from pregnant women and newborns as well as anti-
Toxoplasma
IgG avidity with these three systems on 54 sera from pregnant women with positive IgG and IgM. The IgG and IgM results were in agreement in, respectively, 95.2% and 98.3% (Vidas versus Architect) and 96.9% and 95.3% (Vidas versus Liaison) of the samples. Specificities were excellent for all the assays, while Vidas sensitivities ranged (depending on the classification of gray zone results) from 93.8 to 98.4% for IgG (Architect, 84.4 to 93.8%; Liaison, 93.8%) and from 81.8 to 90.9% for IgM (Architect, 63.6%; Liaison, 81.8 to 90.9%). In seroconversion sequences, IgMs were generally detected simultaneously by the three assays, while Architect was the earliest assay to detect IgG. In noninfected children, maternally transmitted IgGs were detected for a longer time with Architect than with the other systems. IgMs were positive in only one infected child with the Vidas and Liaison systems. Significantly more sera were classified in the high-avidity category with Vidas than with Architect. This evaluation shows similar performances for Vidas and more recent systems. The Vidas system adequately detects toxoplasmosis in pregnant women and newborns. This system fits the needs of laboratories working on small routine series for first-line testing as well as expert laboratories, due to a high specificity and a powerful avidity test.
A Single Dose of a DNA Vaccine Encoding Apa Coencapsulated with 6,6′-Trehalose Dimycolate in Microspheres Confers Long-Term Protection against Tuberculosis in Mycobacterium bovis BCG-Primed Mice
Authors: Carlétti Dyego , Morais da Fonseca Denise , Gembre Ana Flávia , Masson Ana Paula , Weijenborg Campos Lívia , Leite Luciana C. C. , Rodrigues Pires Andréa , Lannes-Vieira Joseli , Lopes Silva Célio , Bonato Vânia Luiza Deperon , Horn Cynthia
Published: June 2013

Mycobacterium bovis
BCG prime DNA (
Mycobacterium tuberculosis
genes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted by
M. tuberculosis
. This study investigated the immune protection of Apa DNA vaccine against intratracheal
M. tuberculosis
challenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carrying
apa
and 6,6′-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.
Development of an Enzyme-Linked Immunosorbent Assay for Serodiagnosis of Ringworm Infection in Cattle
Authors: Băguţ Elena Tatiana , Cambier Ludivine , Heinen Marie-Pierre , Cozma Vasile , Monod Michel , Mignon Bernard
Published: June 2013

The aim of this study was to develop an in-house enzyme-linked immunosorbent assay (ELISA) for the serological diagnosis of ringworm infection in cattle. We used available recombinant forms of
Trichophyton rubrum
dipeptidyl peptidase V (TruDppV) and
T. rubrum
leucin aminopeptidase 2 (TruLap2), which are 98% identical to
Trichophyton verrucosum
orthologues. Field serum samples from 135 cattle with ringworm infection, as confirmed by direct microscopy, fluorescence microscopy, and PCR, and from 55 cattle without any apparent skin lesions or history of ringworm infection that served as negative controls were used. Sensitivities, specificities, and positive and negative predictive values were determined to evaluate the diagnostic value of our ELISA. Overall, the ELISAs based on recombinant TruDppV and TruLap2 discriminated well between infected animals and healthy controls. Highly significant differences (
P
< 0.0001, Mann-Whitney U test) were noted between optical density values obtained when sera from infected versus control cattle were tested. The ELISA developed for the detection of specific antibodies against DppV gave 89.6% sensitivity, 92.7% specificity, a 96.8% positive predictive value, and a 78.4% negative predictive value. The recombinant TruLap2-based ELISA displayed 88.1% sensitivity, 90.9% specificity, a 95.9% positive predictive value, and a 75.7% negative predictive value. To the best of our knowledge, this is the first ELISA based on recombinant antigens for assessing immune responses to ringworm infection in cattle; it is particularly suitable for epidemiological studies and also for the evaluation of vaccines and/or vaccination procedures.
Does Binding of Complement Factor H to the Meningococcal Vaccine Antigen, Factor H Binding Protein, Decrease Protective Serum Antibody Responses?
Authors: Granoff Dan M. , Ram Sanjay , Beernink Peter T.
Published: June 2013

Factor H binding protein (fHbp) is a principal antigen in a multicomponent meningococcal vaccine recently licensed in Europe for prevention of serogroup B diseases. The protein recruits the complement downregulator, factor H (fH), to the bacterial surface, which enables the organism to resist complement-mediated bacteriolysis. Binding is specific for human fH. In preclinical studies, mice and rabbits immunized with fHbp vaccines developed serum bactericidal antibody responses, which in humans predict protection against developing meningococcal disease. These studies, however, were in animals whose fH did not bind to the vaccine antigen. Here we review the immunogenicity of fHbp vaccines in human fH transgenic mice. The data suggest that animals with high serum human fH concentrations have impaired protective antibody responses. Further, mutant fHbp vaccines with single amino acid substitutions that decrease fH binding are superior immunogens, possibly by unmasking epitopes in the fH binding site that are important for eliciting serum bactericidal antibody responses. Humans immunized with fHbp vaccines develop serum bactericidal antibody, but achieving broad coverage in infants required incorporation of additional antigens, including outer membrane vesicles, which increased rates of fever and local reactions at the injection site. The experimental results in transgenic mice predict that fHbp immunogenicity can be improved in humans by using mutant fHbp vaccines with decreased fH binding. These results have important public health implications for developing improved fHbp vaccines for control of serogroup B meningococcal disease and for development of vaccines against other microbes that bind host molecules.
Impact of the Yosemite Hantavirus Outbreak on Hantavirus Antibody Testing at a National Reference Laboratory
Authors: Prince Harry E. , Lieberman Jay M.
Published: June 2013

In conjunction with the 2012 Yosemite hantavirus outbreak, the number of sera our facility tested for hantavirus antibodies increased. We tracked test results and used the data set to determine if a more efficient testing algorithm was possible. Sera were screened using laboratory-developed pan-hantavirus IgG and IgM enzyme immunoassays (EIAs), with an index of >1.10 defined as positive. Sera that were IgM positive by screening (screen IgM
+
) were tested for Sin Nombre virus (SNV)-specific IgM using a laboratory-developed EIA; screen IgM
+
IgG
+
sera were also tested for SNV IgG using a laboratory-developed immunoblot assay. SNV antibody-positive samples were sent to state public health laboratories (PHL) or the CDC for confirmation. Of 3,946 sera tested from July through December 2012, 205 were screen IgM
+
IgG negative (IgG
−
); 7/205 were SNV IgM
+
, but only 1/5 sent to PHL/CDC was confirmed as SNV IgM
+
. Of 61 screen IgM
+
IgG
+
sera, 16 were SNV antibody positive; 13/16 sera (from 11 patients) went to PHL/CDC, where SNV infection was confirmed for all patients. Of 12 confirmed patients, 7 had been exposed at Yosemite. A modified algorithm defining screen indices of ≥2.00 as positive identified 11/12 confirmed cases while reducing the number of sera requiring SNV-specific antibody testing by 65%; the patient missed was not tested until 3 months after the onset of symptoms. Hantavirus antibody testing at our facility identified 12 SNV-infected patients, including 7 exposed at Yosemite. Some screen IgM
+
IgG
−
SNV IgM
+
results were false positives, emphasizing the value of PHL/CDC confirmatory testing. We identified a modified algorithm requiring analysis of fewer specimens for SNV-specific antibodies without loss of sensitivity.
Lagenidium sp. Ocular Infection Mimicking Ocular Pythiosis
Authors: Reinprayoon Usanee , Permpalung Nitipong , Kasetsuwan Ngamjit , Plongla Rongpong , Mendoza Leonel , Chindamporn Ariya
Published: June 2013

This is a report of a
Lagenidium
sp. in a Thai patient who was diagnosed with severe keratitis that was unresponsive to antibacterial and antifungal drugs. Examination of a corneal biopsy specimen confirmed the presence of aseptate hyphae. The internal transcribed spacer DNA sequence of the strain isolated showed 97% identity with
Lagenidium giganteum
and other
Lagenidium
species.
Surface Microbes in the Neonatal Intensive Care Unit: Changes with Routine Cleaning and over Time
Authors: Bokulich Nicholas A. , Mills David A. , Underwood Mark A.
Published: June 2013

Premature infants in neonatal intensive care units (NICUs) are highly susceptible to infection due to the immaturity of their immune systems, and nosocomial infections are a significant risk factor for death and poor neurodevelopmental outcome in this population. To investigate the impact of cleaning within a NICU, a high-throughput short-amplicon-sequencing approach was used to profile bacterial and fungal surface communities before and after cleaning. Intensive cleaning of surfaces in contact with neonates decreased the total bacterial load and the percentage of
Streptococcus
species with similar trends for total fungal load and
Staphylococcus
species; this may have clinical relevance since staphylococci and streptococci are the most common causes of nosocomial NICU infections. Surfaces generally had low levels of other taxa containing species that commonly cause nosocomial infections (e.g.,
Enterobacteriaceae
) that were not significantly altered with cleaning. Several opportunistic yeasts were detected in the NICU environment, demonstrating that these NICU surfaces represent a potential vector for spreading fungal pathogens. These results underline the importance of routine cleaning as a means of managing the microbial ecosystem of NICUs and of future opportunities to minimize exposures of vulnerable neonates to potential pathogens and to use amplicon-sequencing tools for microbial surveillance and hygienic testing in hospital environments.
Emerging Escherichia Pathogen
Authors: Kaewpoowat Quanhathai , Permpalung Nitipong , Sentochnik Deborah E.
Published: June 2013

Escherichia hermannii
was first identified as a new species in 1982. It has rarely been reported as a human pathogen. We report the first case of
E. hermannii
as the sole pathogen in a catheter-related bloodstream infection.
Multilocus Sequence Analysis Provides Insights into Molecular Epidemiology of Chlamydia pecorum Infections in Australian Sheep, Cattle, and Koalas
Authors: Jelocnik Martina , Frentiu Francesca D. , Timms Peter , Polkinghorne Adam
Published: June 2013

Chlamydia pecorum
is a significant pathogen of domestic livestock and wildlife. We have developed a
C. pecorum
-specific multilocus sequence analysis (MLSA) scheme to examine the genetic diversity of and relationships between Australian sheep, cattle, and koala isolates. An MLSA of seven concatenated housekeeping gene fragments was performed using 35 isolates, including 18 livestock isolates (11 Australian sheep, one Australian cow, and six U.S. livestock isolates) and 17 Australian koala isolates. Phylogenetic analyses showed that the koala isolates formed a distinct clade, with limited clustering with
C. pecorum
isolates from Australian sheep. We identified 11 MLSA sequence types (STs) among Australian
C. pecorum
isolates, 10 of them novel, with koala and sheep sharing at least one identical ST (designated ST2013Aa). ST23, previously identified in global
C. pecorum
livestock isolates, was observed here in a subset of Australian bovine and sheep isolates. Most notably, ST23 was found in association with multiple disease states and hosts, providing insights into the transmission of this pathogen between livestock hosts. The complexity of the epidemiology of this disease was further highlighted by the observation that at least two examples of sheep were infected with different
C. pecorum
STs in the eyes and gastrointestinal tract. We have demonstrated the feasibility of our MLSA scheme for understanding the host relationship that exists between Australian
C. pecorum
strains and provide the first molecular epidemiological data on infections in Australian livestock hosts.
Landscape of DNA Virus Associations across Human Malignant Cancers: Analysis of 3,775 Cases Using RNA-Seq
Authors: Khoury Joseph D. , Tannir Nizar M. , Williams Michelle D. , Chen Yunxin , Yao Hui , Zhang Jianping , Thompson Erika J. ,   the TCGA Network, Meric-Bernstam Funda , Medeiros L. Jeffrey , Weinstein John N. , Su Xiaoping
Published: June 2013

Elucidation of tumor-DNA virus associations in many cancer types has enhanced our knowledge of fundamental oncogenesis mechanisms and provided a basis for cancer prevention initiatives. RNA-Seq is a novel tool to comprehensively assess such associations. We interrogated RNA-Seq data from 3,775 malignant neoplasms in The Cancer Genome Atlas database for the presence of viral sequences. Viral integration sites were also detected in expressed transcripts using a novel approach. The detection capacity of RNA-Seq was compared to available clinical laboratory data. Human papillomavirus (HPV) transcripts were detected using RNA-Seq analysis in head-and-neck squamous cell carcinoma, uterine endometrioid carcinoma, and squamous cell carcinoma of the lung. Detection of HPV by RNA-Seq correlated with detection by
in situ
hybridization and immunohistochemistry in squamous cell carcinoma tumors of the head and neck. Hepatitis B virus and Epstein-Barr virus (EBV) were detected using RNA-Seq in hepatocellular carcinoma and gastric carcinoma tumors, respectively. Integration sites of viral genes and oncogenes were detected in cancers harboring HPV or hepatitis B virus but not in EBV-positive gastric carcinoma. Integration sites of expressed viral transcripts frequently involved known coding areas of the host genome. No DNA virus transcripts were detected in acute myeloid leukemia, cutaneous melanoma, low- and high-grade gliomas of the brain, and adenocarcinomas of the breast, colon and rectum, lung, prostate, ovary, kidney, and thyroid. In conclusion, this study provides a large-scale overview of the landscape of DNA viruses in human malignant cancers. While further validation is necessary for specific cancer types, our findings highlight the utility of RNA-Seq in detecting tumor-associated DNA viruses and identifying viral integration sites that may unravel novel mechanisms of cancer pathogenesis.
Characterization of a Discontinuous Neutralizing Epitope on Glycoprotein B of Human Cytomegalovirus
Authors: Spindler Nadja , Rücker Pia , Pötzsch Sonja , Diestel Uschi , Sticht Heinrich , Martin-Parras Luis , Winkler Thomas H. , Mach Michael
Published: June 2013

Human cytomegalovirus (HCMV) is a ubiquitously distributed pathogen that causes severe disease in immunosuppressed patients and newborn infants infected
in utero
. The viral envelope glycoprotein B (gB) is an attractive molecule for active vaccination and passive immunoprophylaxis and therapy. Using human monoclonal antibodies (MAbs), we have recently identified antigenic region 4 (AD-4) on gB as an important target for neutralizing antibodies. AD-4 is formed by a discontinuous sequence comprising amino acids 121 to 132 and 344 to 438 of gB of HCMV strain AD169. To map epitopes for human antibodies on this protein domain, we used a three-dimensional (3D) model of HCMV gB to identify surface-exposed amino acids on AD-4 and selected juxtaposed residues for alanine scans. A tyrosine (Y) at position 364 and a lysine (K) at position 379 (the YK epitope), which are immediate neighbors on the AD-4 surface, were found to be essential for binding of the human MAbs. Recognition of AD-4 by sera from HCMV-infected individuals also was largely dependent on these two residues, indicating a general importance for the antibody response against AD-4. A panel of AD-4 recombinant viruses harboring mutations at the crucial antibody binding sites was generated. The viruses showed significantly reduced susceptibility to neutralization by AD-4-specific MAbs or polyclonal AD-4-specific antibodies, indicating that the YK epitope is dominant for the AD-4-specific neutralizing antibody response during infection. To our knowledge, this is the first molecular identification of a functional discontinuous epitope on HCMV gB. Induction of antibodies specific for this epitope may be a desirable goal following vaccination with gB.
N-Linked Glycosylation of the Hemagglutinin Protein Influences Virulence and Antigenicity of the 1918 Pandemic and Seasonal H1N1 Influenza A Viruses
Authors: Sun Xiangjie , Jayaraman Akila , Maniprasad Pavithra , Raman Rahul , Houser Katherine V. , Pappas Claudia , Zeng Hui , Sasisekharan Ram , Katz Jacqueline M. , Tumpey Terrence M.
Published: June 2013

The hemagglutinin (HA) protein is a major virulence determinant for the 1918 pandemic influenza virus; however, it encodes no known virulence-associated determinants. In comparison to seasonal influenza viruses of lesser virulence, the 1918 H1N1 virus has fewer glycosylation sequons on the HA globular head region. Using site-directed mutagenesis, we found that a 1918 HA recombinant virus, of high virulence, could be significantly attenuated in mice by adding two additional glycosylation sites (asparagine [Asn] 71 and Asn 286) on the side of the HA head. The 1918 HA recombinant virus was further attenuated by introducing two additional glycosylation sites on the top of the HA head at Asn 142 and Asn 172. In a reciprocal experimental approach, deletion of HA glycosylation sites (Asn 142 and Asn 177, but not Asn 71 and Asn 104) from a seasonal influenza H1N1 virus, A/Solomon Islands/2006 (SI/06), led to increased virulence in mice. The addition of glycosylation sites to 1918 HA and removal of glycosylation sites from SI/06 HA imposed constraints on the theoretical structure surrounding the glycan receptor binding sites, which in turn led to distinct glycan receptor binding properties. The modification of glycosylation sites for the 1918 and SI/06 viruses also caused changes in viral antigenicity based on cross-reactive hemagglutinin inhibition antibody titers with antisera from mice infected with wild-type or glycan mutant viruses. These results demonstrate that glycosylation patterns of the 1918 and seasonal H1N1 viruses directly contribute to differences in virulence and are partially responsible for their distinct antigenicity.
Quantitative Comparison of Human Parainfluenza Virus Hemagglutinin-Neuraminidase Receptor Binding and Receptor Cleavage
Authors: Tappert Mary M. , Porterfield J. Zachary , Mehta-D'Souza Padmaja , Gulati Shelly , Air Gillian M.
Published: June 2013

The human parainfluenza virus (hPIV) hemagglutinin-neuraminidase (HN) protein binds (H) oligosaccharide receptors that containN-acetylneuraminic acid (Neu5Ac) and cleaves (N) Neu5Ac from these oligosaccharides. In order to determine if one of HN′s two functions is predominant, we measured the affinity of H for its ligands by a solid-phase binding assay with two glycoprotein substrates and by surface plasmon resonance with three monovalent glycans. We compared the dissociation constant (Kd) values from these experiments with previously determined Michaelis-Menten constants (Kms) for the enzyme activity. We found that glycoprotein substrates and monovalent glycans containing Neu5Acα2-3Galβ1-4GlcNAc bind HN withKdvalues in the 10 to 100 μM range.Kmvalues for HN were previously determined to be on the order of 1 mM (M. M. Tappert, D. F. Smith, and G. M. Air, J. Virol. 85:12146–12159, 2011). AKmvalue greater than theKdvalue indicates that cleavage occurs faster than the dissociation of binding and will dominate under N-permissive conditions. We propose, therefore, that HN is a neuraminidase that can hold its substrate long enough to act as a binding protein. The N activity can therefore regulate binding by reducing virus-receptor interactions when the concentration of receptor is high.
Pyrrolidine Dithiocarbamate Inhibits Herpes Simplex Virus 1 and 2 Replication, and Its Activity May Be Mediated through Dysregulation of the Ubiquitin-Proteasome System
Authors: Qiu Min , Chen Yu , Cheng Lin , Chu Ying , Song Hong-Yong , Wu Zhi-Wei
Published: June 2013

Pyrrolidine dithiocarbamate (PDTC) is widely used as an antioxidant or an NF-κB inhibitor. It has been reported to inhibit the replication of human rhinoviruses, poliovirus, coxsackievirus, and influenza virus. In this paper, we report that PDTC could inhibit the replication of herpes simplex virus 1 and 2 (HSV-1 and HSV-2). PDTC suppressed the expression of HSV-1 and HSV-2 viral immediate early (IE) and late (membrane protein gD) genes and the production of viral progeny. This antiviral property was mediated by the dithiocarbamate moiety of PDTC and required the presence of Zn2+. Although PDTC could potently block reactive oxygen species (ROS) generation, it was found that this property did not contribute to its anti-HSV activity. PDTC showed no activity in disrupting the mitogen-activated protein kinase (MAPK) pathway activation induced by viral infection that was vital for the virus's propagation. We found that PDTC modulated cellular ubiquitination and, furthermore, influenced HSV-2-induced IκB-α degradation to inhibit NF-κB activation and enhanced PML stability in the nucleus, resulting in the inhibition of viral gene expression. These results suggested that the antiviral activity of PDTC might be mediated by its dysregulation of the cellular ubiquitin-proteasome system (UPS).
HIV-1 Gag Cytotoxic T Lymphocyte Epitopes Vary in Presentation Kinetics Relative to HLA Class I Downregulation
Authors: Balamurugan Arumugam , Ali Ayub , Boucau Julie , Le Gall Sylvie , Ng Hwee L. , Yang Otto O.
Published: June 2013

Although CD8
+
cytotoxic T lymphocytes (CTLs) are protective in HIV-1 infection, the factors determining their antiviral efficiency are poorly defined. It is proposed that Gag targeting is superior because of very early Gag epitope presentation, allowing early killing of infected cells before Nef-mediated downregulation of human leukocyte antigen class I (HLA-I). To study Gag epitope presentation kinetics, three epitopes (SL9
77-85
, KF11
162-172
, and TW10
240-249
) were genetically translocated from their endogenous location in the Rev-dependent (late)
gag
gene into the Rev-independent (early)
nef
gene with concomitant mutation of the corresponding endogenous epitopes to nonrecognized sequences. These viruses were compared to the index virus for CTL-mediated suppression of replication and the susceptibility of this antiviral activity to Nef-mediated HLA-I downregulation. SL9-specific CTLs gained activity after SL9 translocation to Nef, going from Nef sensitive to Nef insensitive, indicating that translocation accelerated infected cell recognition from after to before HLA-I downregulation. KF11-specific CTL antiviral activity was unchanged and insensitive to HLA-I downregulation before and after KF11 translocation, suggesting that already rapid recognition of infected cells was not accelerated. However, TW10-specific CTLs that were insensitive to Nef at the baseline became sensitive with reduced antiviral activity after translocation, indicating that translocation retarded epitope expression. Cytosolic peptide processing assays suggested that TW10 was inefficiently generated after translocation to Nef, compared to SL9 and KF11. As a whole, these data demonstrate that epitope presentation kinetics play an important role in CTL antiviral efficiency, that Gag epitopes are not uniformly presented early, and that the epitope context can play a major role in presentation kinetics.
A Mutation in the Stalk of the Newcastle Disease Virus Hemagglutinin-Neuraminidase (HN) Protein Prevents Triggering of the F Protein despite Allowing Efficient HN-F Complex Formation
Authors: Mirza Anne M. , Iorio Ronald M.
Published: June 2013

Newcastle disease virus (NDV)-induced membrane fusion requires formation of a complex between the hemagglutinin-neuraminidase (HN) and fusion (F) proteins. Substitutions for NDV HN stalk residues A89, L90, and L94 block fusion by modulating formation of the HN-F complex. Here, we demonstrate that a nearby L97A substitution, though previously shown to block fusion, allows efficient HN-F complex formation and likely acts by preventing changes in the HN stalk required for triggering of the bound F protein.
A Role for Ifit2 in Restricting West Nile Virus Infection in the Brain
Authors: Cho Hyelim , Shrestha Bimmi , Sen Ganes C. , Diamond Michael S.
Published: June 2013

Previous studies have demonstrated that type I interferon (IFN-I) restricts West Nile virus (WNV) replication and pathogenesis in peripheral and central nervous system (CNS) tissues. However, thein vivorole of specific antiviral genes that are induced by IFN-I against WNV infection remains less well characterized. Here, usingIfit2−/−mice, we defined the antiviral function of the interferon-stimulated gene (ISG)Ifit2in limiting infection and diseasein vivoby a virulent North American strain of WNV. Compared to congenic wild-type controls,Ifit2−/−mice showed enhanced WNV infection in a tissue-restricted manner, with preferential replication in the CNS of animals lackingIfit2. Virological analysis of cultured macrophages, dendritic cells, fibroblasts, cerebellar granule cell neurons, and cortical neurons revealed cell type-specific antiviral functions of Ifit2 against WNV. In comparison, small effects of Ifit2 were observed on the induction or magnitude of innate or adaptive immune responses. Our results suggest that Ifit2 restricts WNV infection and pathogenesis in different tissues in a cell type-specific manner.
Possible Role of a Cell Surface Carbohydrate in Evolution of Resistance to Viral Infections in Old World Primates
Authors: Rodriguez Idalia A. , Welsh Raymond M.
Published: June 2013

Due to inactivation of the α1,3-galactosyltransferase gene (GGTA1, or the α1,3GT gene) approximately 28 million years ago, the carbohydrate αGal (Galα1,3Galβ1,4GlcNAc) is not expressed on the cells of Old World monkeys and apes (including humans) but is expressed in all other mammals. The proposed selective advantage of this mutation for these primates is the ability to produce anti-Gal antibodies, which may be an effective immune component in neutralizing αGal-expressing pathogens. However, loss of α1,3GT expression may have been advantageous by providing natural resistance against viral pathogens that exploited the α1,3GT pathway or cell surface αGal for infection. Infections of paired cell lines with differential expression of α1,3GT showed that Sindbis viruses (SINV) preferentially replicate in α1,3GT-positive cells, whereas herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2) preferentially grow in cells lacking α1,3GT. Viral growth and spread correlated with the ability of the different viruses to successfully initiate infection in the presence or absence of α1,3GT expression. GT knockout (KO) suckling mice infected with SINV strains (AR339 and S.A.AR86) experienced significant delay in onset of disease symptoms and mortality compared to wild-type (WT) B6 suckling mice. In contrast, HSV-2-infected GT KO mice had higher viral titers in spleen and liver and exhibited significantly more focal hepatic necrosis than WT B6 mice. This study demonstrates that α1,3GT activity plays a role in the course of infections for certain viruses. Furthermore, this study has implications for the evolution of resistance to viral infections in primates.
Positively Charged Residues at the Five-Fold Symmetry Axis of Cell Culture-Adapted Foot-and-Mouth Disease Virus Permit Novel Receptor Interactions
Authors: Berryman Stephen , Clark Stuart , Kakker Naresh K. , Silk Rhiannon , Seago Julian , Wadsworth Jemma , Chamberlain Kyle , Knowles Nick J. , Jackson Terry
Published: June 2013

Field isolates of foot-and-mouth disease virus (FMDV) have a restricted cell tropism which is limited by the need for certain RGD-dependent integrin receptors. In contrast, cell culture-adapted viruses use heparan sulfate (HS) or other unidentified molecules as receptors to initiate infection. Here, we report several novel findings resulting from cell culture adaptation of FMDV. In cell culture, a virus with the capsid of the A/Turkey/2/2006 field isolate gained the ability to infect CHO and HS-deficient CHO cells as a result of a single glutamine (Q)-to-lysine (K) substitution at VP1-110 (VP1-
Q
110
K
). Using site-directed mutagenesis, the introduction of lysine at this same site also resulted in an acquired ability to infect CHO cells by type O and Asia-1 FMDV. However, this ability appeared to require a second positively charged residue at VP1-109. CHO cells express two RGD-binding integrins (α5β1 and αvβ5) that, although not used by FMDV, have the potential to be used as receptors; however, viruses with the VP1-
Q
110
K
substitution did not use these integrins. In contrast, the VP1-
Q
110
K
substitution appeared to result in enhanced interactions with αvβ6, which allowed a virus with KGE in place of the normal RGD integrin-binding motif to use αvβ6 as a receptor. Thus, our results confirmed the existence of nonintegrin, non-HS receptors for FMDV on CHO cells and revealed a novel, non-RGD-dependent use of αvβ6 as a receptor. The introduction of lysine at VP1-110 may allow for cell culture adaptation of FMDV by design, which may prove useful for vaccine manufacture when cell culture adaptation proves intractable.
LateStreptococcus bovisinfection of total knee replacement complicated by infective endocarditis and associated with colonic ulcers
Authors: Nagy Mathias Thomas , Hla Sann Minn , Keys Graham Watson
Published: June 2013

Streptococcus bovisis rare cause of late infections after total knee replacement (TKR). This report presents a case of confirmed late septic arthritis following TKR caused byS bovisthat was further complicated with infective endocarditis resulting in aortic valve insufficiency in an immunecompetent patient. As an association betweenS bovisand gastrointestinal malignancies is suggested, a workup for such malignancies was performed that revealed non-malignant ulcers in patient's ascending colon. The patient is currently recovering from his aortic valve replacement surgery and is scheduled to have annual colonoscopies. His knee joint has improved; however, he developed constant pain because of underlying chronic infection in the affected joint and has difficulties mobilising. Therefore, a revision TKR is considered but postponed until he fully recovers from his heart valve surgery.
Cardiopulmonary complications in a patient with bezoar
Authors: Viveiros Eulália , Moniz Marta , Nunes Pedro , Silvestre Catarina
Published: June 2013

We report a case of a 17-year-old institutionalised male with a medical history of fragile X syndrome, bilateral congenital glaucoma, cataracts and pica disorder. He was transferred to our paediatric intensive care unit owing to respiratory failure and hypotension. On transoesophageal echocardiogram, he presented left atrium compression. A CT of the thorax and mediastinum revealed an unknown heterogeneous material in the lumen of the stomach and oesophagus, with a lung parenchyma suggestive of alveolar foreign material. Endoscopic evaluation showed diaper fragments inside the oesophagus and stomach. Fragmentation and suction of diaper material was made. Medical treatment was performed with inotropic support, conventional mechanical ventilation and antibiotics.
Bleomycin-induced flagellate hyperpigmentation
Authors: Resende Cristina , Araújo Catarina , Gomes Joana , Brito Celeste
Published: June 2013

Bleomycin is a chemotherapeutic agent used in the treatment of different tumours. It has several side effects, including flagellate hyperpigmentation, which is a unique and a well-documented side effect of bleomycin therapy. We report a case of a 23-year-old woman with a personal history of ovarian dysgerminoma, who developed flagellate hyperpigmentation on trunk after bleomycin therapy.
Cranberry impairs selected behaviors essential for virulence inProteus mirabilisHI4320
Authors: McCall Jennifer , Hidalgo Gabriela , Asadishad Bahareh , Tufenkji Nathalie
Published: June 2013

Proteus mirabilis is an etiological agent of complicated urinary tract infections. North American cranberries (Vaccinium macrocarpon) have long been considered to have protective properties against urinary tract infections. This work reports the effects of cranberry powder (CP) on the motility of P. mirabilis HI4320 and its expression of flaA, flhD, and ureD. Our results show that swimming and swarming motilities and swarmer-cell differentiation were inhibited by CP. Additionally, transcription of the flagellin gene flaA and of flhD, the first gene of the flagellar master operon flhDC, decreased during exposure of P. mirabilis to various concentrations of CP. Moreover, using ureD–gfp, a fusion of the urease accessory gene ureD with gfp, we show that CP inhibits urease expression. Because we demonstrate that CP does not inhibit the growth of P. mirabilis, the observed effects are not attributable to toxicity. Taken together, our results demonstrate that CP hinders motility of P. mirabilis and reduces the expression of important virulence factors.
Supersymmetric models on AdS3 and AdS4 embedding superspaces
Authors: McKeon D.G.C.
Published: June 2013

Superspace techniques are used to formulate a supersymmetric model on an AdS3 surface embedded in four dimensions. In this model, the supersymmetry transformation is the “square root” of the transformation generated by the isometry generators of AdS3. Because momentum is not an isometry generator, supersymmetry does not result in equal masses for a bosonic field and its fermionic partner. We express this model in terms of coordinates that characterize the AdS3 space. In one coordinate system, it is possible to define a subspace with a Minkowski metric. It becomes possible to infer a model in AdS4 space in which there is a symmetry transformation that relates bosonic and fermionic fields. This model is not a consequence of being formulated in a superspace and the fermionic symmetry transformation is not the “square root” of an isometry of AdS4.
A STUDY ON ANISOTROPY IN THE ARRIVAL DIRECTIONS OF ULTRA-HIGH-ENERGY COSMIC RAYS OBSERVED BY PIERRE AUGER OBSERVATORY
Authors: KIM HANG BAE
Published: June 2013

We study the anisotropy in the arrival directions of Pierre Auger Observatory (PAO) ultra-high-energy cosmic rays (UHECRs), using the point source correlational angular distance distribution (CADD). The result shows that the anisotropy is characterized by one prominent excess region and one void region. The excess region is located near the Centaurus A direction, supporting that the Centaurus A is a promising UHECR source. The void region near the south pole direction may be used to limit the diffuse isotropic background contribution.
EFFECT FROM THE GLUON-FUSION SIGNAL AND BACKGROUND INTERFERENCE FOR HIGGS DECAYING TO γγ ANALYSIS AT THE LHC
Authors: TAO JUN-QUAN , SHEN YU-QIAO , FAN JIA-WEI , XIAO HONG , CHEN GUO-MING , CHEN HE-SHENG , BIAN JIAN-GUO , CHEN YE , LIANG SONG , MENG XIANG-WEI , MUHAMMAD AHMAD , SARMADMASOOD SHAHEEN , WANG ZHENG , ZHU SHI-HAI
Published: June 2013

We calculate the destructive interference factors between the Higgs decay H→γγ produced in gluon-fusion and the Standard Model (SM) continuum gg→γγ process, as a function of the scattering angle in the center-of-mass frame of the final two photons. The interference factors are studied with the selections based on the acceptance criteria of the ATLAS and CMS H→γγ searches at the LHC. The result shows that the destructive interference is only at an order of 2.5% for the SM Higgs analysis at the LHC. The factors are almost the same for the same Higgs mass hypothesis but with different proton–proton collisions at [Formula: see text], 8 TeV, 13 TeV and 14 TeV. The destructive interference is far below the present uncertainty on the total cross-section prediction of Higgs, which is about 15% used at the LHC. A destructive interference factor of -2.5% is suggested to be used in the H→γγ analysis at the LHC, due to the effect from the interference for this decay channel.
STEERABILITY OF HERMITE KERNEL
Authors: YANG BO , FLUSSER JAN , SUK TOMÁŠ
Published: June 2013

Steerability is a useful and important property of "kernel" functions. It enables certain complicated operations involving orientation manipulation on images to be executed with high efficiency. Thus, we focus our attention on the steerability of Hermite polynomials and their versions modulated by the Gaussian function with different powers, defined as the Hermite kernel. Certain special cases of such kernel, Hermite polynomials, Hermite functions and Gaussian derivatives are discussed in detail. Correspondingly, these cases demonstrate that the Hermite kernel is a powerful and effective tool for image processing. Furthermore, the steerability of the Hermite kernel is proved with the help of a property of Hermite polynomials revealing the rule concerning the product of two Hermite polynomials after coordination rotation. Consequently, any order of the Hermite kernel inherits steerability. Moreover, a couple sets of an explicit interpolation function and basis function can be directly obtained. We provide some examples to verify steerability of the Hermite kernel. Experimental results show the effectiveness of steerability and its potential applications in the fields of image processing and computer vision.
A RECOMMENDATION SYSTEM FOR ANTI-DIABETIC DRUGS SELECTION BASED ON FUZZY REASONING AND ONTOLOGY TECHNIQUES
Authors: CHEN SHYI-MING , HUANG YUN-HOU , CHEN RUNG-CHING
Published: June 2013

Diabetes mellitus is a common chronic disease in recent years. According to the World Health Organization, the estimated number of diabetic patients will increase 56% in Asia from the year 2010 to 2025, where the number of anti-diabetic drugs that doctors are able to utilize also increase as the development of pharmaceutical drugs. In this paper, we present a recommendation system for anti-diabetic drugs selection based on fuzzy reasoning and ontology techniques, where fuzzy rules are used to represent knowledge to infer the usability of the classes of anti-diabetic drugs based on fuzzy reasoning techniques. We adopt the "Medical Guidelines for Clinical Practice for the Management of Diabetes Mellitus" provided by the American Association of Clinical Endocrinologists to build the ontology knowledge base. The experimental results show that the proposed anti-diabetic drugs recommendation system gets the same accuracy rate as the one of Chen et al.'s method (R. C. Chen, Y. H. Huang, C. T. Bau and S. M. Chen, Expert Syst. Appl.39(4) (2012) 3995–4006.) and it is better than Chen et al.'s method (R. C. Chen, Y. H. Huang, C. T. Bau and S. M. Chen, Expert Syst. Appl.39(4) (2012) 3995–4006.) due to the fact that it can deal with the semantic degrees of patients' tests and can provide different recommend levels of anti-diabetic drugs. It provides us with a useful way for anti-diabetic drugs selection based on fuzzy reasoning and ontology techniques.
ALGORITHMIC CONSTRUCTION OF EXACT SOLUTIONS FOR NEUTRAL STATIC PERFECT FLUID SPHERES
Authors: HANSRAJ SUDAN , KRUPANANDAN DANIEL
Published: June 2013

Although it ranks amongst the oldest of problems in classical general relativity, the challenge of finding new exact solutions for spherically symmetric perfect fluid spacetimes is still ongoing because of a paucity of solutions which exhibit the necessary qualitative features compatible with observational evidence. The problem amounts to solving a system of three partial differential equations in four variables, which means that any one of four geometric or dynamical quantities must be specified at the outset and the others should follow by integration. The condition of pressure isotropy yields a differential equation that may be interpreted as second-order in one of the space variables or also as first-order Ricatti type in the other space variable. This second option has been fruitful in allowing us to construct an algorithm to generate a complete solution to the Einstein field equations once a geometric variable is specified ab initio. We then demonstrate the construction of previously unreported solutions and examine these for physical plausibility as candidates to represent real matter. In particular we demand positive definiteness of pressure, density as well as a subluminal sound speed. Additionally, we require the existence of a hypersurface of vanishing pressure to identify a radius for the closed distribution of fluid. Finally, we examine the energy conditions. We exhibit models which display all of these elementary physical requirements.
ANALYTICAL SOLUTIONS OF BIO-HEAT CONDUCTION ON SKIN IN FOURIER AND NON-FOURIER MODELS
Authors: LIN SHUEEI-MUH
Published: June 2013

In general, the transport of thermal energy in living tissue is a complex process. The analysis of the heat conduction of skin tissue is helpful for understanding of the bio-thermo-mechanical behavior of skin tissue. So far, three kinds of conduction law — (1) the Fourier model, (2) the C-V model and (3) dual-phase-lag (DPL) model — are often investigated in bio-thermal transfer process. In this study, the mathematical model of heat conduction of the skin tissue subjected to a general transient heating at the skin surface was established. The analytical solutions of these three conduction models are presented. In addition, the measure of thermal injury of the skin tissue subjected to a harmonic heating was investigated. It was found that the phenomenon of Fourier model is greatly different to those of the C-V and DPL models. Moreover, the effects of the phase lags, the heating frequency, and the heat quantity on the temperature variation and the index of thermal injury were significant. In sum, the analytical method can be used to solve the conduction problem of any one-layer tissue.