bluuebunny/crossref_metadata_2025 huggingface dataset:
Transforming Fusions of
FGFR
and
TACC
Genes in Human Glioblastoma
Authors: Singh Devendra , Chan Joseph Minhow , Zoppoli Pietro , Niola Francesco , Sullivan Ryan , Castano Angelica , Liu Eric Minwei , Reichel Jonathan , Porrati Paola , Pellegatta Serena , Qiu Kunlong , Gao Zhibo , Ceccarelli Michele , Riccardi Riccardo , Brat Daniel J. , Guha Abhijit , Aldape Ken , Golfinos John G. , Zagzag David , Mikkelsen Tom , Finocchiaro Gaetano , Lasorella Anna , Rabadan Raul , Iavarone Antonio
Published: July 2012

Oncogenic TACC-tics

Human cancers exhibit many types of genomic rearrangements—including some that juxtapose sequences from two unrelated genes—thereby creating fusion proteins with oncogenic activity. Functional analysis of these fusion genes can provide mechanistic insights into tumorigenesis and potentially lead to effective drugs, as famously illustrated by the
BCR-ABL
gene in chronic myelogenous leukemia.

Singh
et al.

(p.
1231
, published online 26 July) identify and characterize a fusion gene present in 3% of human glioblastomas, a deadly brain cancer. In the resultant fusion protein, the tyrosine kinase region of the fibroblast growth factor receptor (FGFR) is joined to a domain from a transforming acidic coiled-coil (TACC) protein. The TACC-FGFR protein is oncogenic, shows unregulated kinase activity, localizes to the mitotic spindle, and disrupts chromosome segregation. In mice, FGFR inhibitors slowed the growth of tumors driven by the TACC-FGFR gene, suggesting that a subset of glioblastoma patients may benefit from these types of drugs.
UV Dosage Levels in Summer: Increased Risk of Ozone Loss from Convectively Injected Water Vapor
Authors: Anderson James G. , Wilmouth David M. , Smith Jessica B. , Sayres David S.
Published: July 2012

Water In, Ozone Out

The danger of stratospheric ozone loss burst into public awareness in the 1980s, when the Antarctic ozone hole was discovered and described. Since then, the specter of ozone depletion in other locations, notably the Arctic, has been identified. Ozone loss is not confined to high latitudes, however, nor is it only the result of the addition of anthropogenic compounds containing chlorine and bromine in the stratosphere, as

Anderson
et al.

(p.
835
, published online 26 July; see the Perspective by

Ravishankara

) now demonstrate. Data from the atmosphere above the continental United States revealed that convective injection of water vapor into the stratosphere affects the free radical chemistry involving the (mostly anthropogenic) chlorine and bromine, thus accelerating ozone loss. This process could become important in the stratospheric ozone budget if the frequency and intensity of these water-injection events, which are most common in the summer, increase as a result of global warming.
Compartmentalized Control of Skin Immunity by Resident Commensals
Authors: Naik Shruti , Bouladoux Nicolas , Wilhelm Christoph , Molloy Michael J. , Salcedo Rosalba , Kastenmuller Wolfgang , Deming Clayton , Quinones Mariam , Koo Lily , Conlan Sean , Spencer Sean , Hall Jason A. , Dzutsev Amiran , Kong Heidi , Campbell Daniel J. , Trinchieri Giorgio , Segre Julia A. , Belkaid Yasmine
Published: July 2012

Skin Specifics

Much of the recent attention paid to the trillions of bacteria that colonize our bodies has been given to the bacteria that reside in the gut.

Naik
et al.

(p.
1115
, published online 26 July) report that colonization of the skin with commensal bacteria is important for tuning effector T cell responses in the skin and for protective immunity against cutaneous infection with the parasite
Leishmania major
in mice. In contrast, selective depletion of the gut microbiota, which plays an important role in modulating immune responses in the gut, had no impact on T cell responses in the skin.
Rapid Detection and Identification of Aspergillus from Lower Respiratory Tract Specimens by Use of a Combined Probe–High-Resolution Melting Analysis
Authors: Alonso María , Escribano Pilar , Guinea Jesus , Recio Sandra , Simon Ainhoa , Peláez Teresa , Bouza Emilio , García de Viedma Darío
Published: July 2012

Diagnosis of invasive aspergillosis (IA) requires increasingly rapid molecular methods that enable sensitive detection and discrimination between species. We designed and evaluated a real-time PCR-based method that combined melting temperature (

T
m

) calling analysis of a specific probe with high-resolution melting analysis of the full amplicon. The test correctly identified 78 isolates of
Aspergillus
section
Fumigati
and non-
Fumigati
sections of
Aspergillus
with a limit of detection of 10
2
conidia/ml (10
2
fg/ml). No cross-reactivity with other fungi was found. The assay was further validated on lower respiratory tract specimens containing
Aspergillus
or not. It successfully identified
Aspergillus
to section level in 56 of 59 specimens. With culture as the gold standard, our assay shows 100% sensitivity and specificity and constitutes an efficient alternative for identification of
Aspergillus
in lower respiratory tract samples.
Prevalence of Streptococcus pneumoniae in Respiratory Samples from Patients with Tracheostomy in a Long-Term-Care Facility
Authors: Adler Amos , Ben-David Debby , Schwaber Mitchell J. , Masarwa Samira , Schwartz David , Porat Nurith , Kotlovsky Tali , Shklyar Maya , Polivkin Nikolay , Weinberg Irina , Lazary Avraham , Ohana Nissim , Dagan Ron
Published: July 2012

We aimed to study the prevalence of
Streptococcus pneumoniae
in respiratory samples from institutionalized patients with chronic tracheostomy. A total of 264 pairs of nasopharyngeal and endotracheal cultures were collected. There was no difference in the proportion of positive cultures between children (21%) and adults (18%). However, the proportion of positive endotracheal cultures was higher than that of nasopharyngeal cultures in adults (18% versus 3%, respectively;
P
< 0.001) but not in children (17% in both sites).
Abundant Drug-Resistant NS3 Mutants Detected by Deep Sequencing in Hepatitis C Virus-Infected Patients Undergoing NS3 Protease Inhibitor Monotherapy
Authors: Svarovskaia Evguenia S. , Martin Ross , McHutchison John G. , Miller Michael D. , Mo Hongmei
Published: July 2012

The high genetic variation of hepatitis C virus (HCV) results in rapid selection of drug resistance mutations (DRMs) during monotherapy with direct-acting antivirals (DAAs). It has been proposed that each possible single mutant preexists in infected individuals; however, the levels of preexisting DRMs are too low to be directly quantified in most patients using current techniques. In this study, we evaluated the presence of DRMs in HCV-infected patients treated with the HCV protease inhibitors GS-9256 or GS-9451 as monotherapy using deep sequencing in 137 longitudinal samples from 45 patients. Software was developed to analyze deep-sequencing results with an assay cutoff of 0.25%. No NS3 DRMs that confer resistance to GS-9256 and GS-9451 (R155K, A156T, and D168V/E) were observed in 33 baseline samples at >0.25%. In contrast, these and other substitutions at NS3 positions 155, 156, and 168 were detected in 19/27 patients at day 2 (24 h) and 21/21 at day 4 (84 h) of monotherapy but not in placebo-treated patients. Based on the DRM growth kinetics during drug treatment, pretreated NS3 mutations at amino acids 155, 156, and 168 were estimated on average at 0.025% and 0.015% per genotype 1a and 1b HCV-infected patients, respectively. Relative fitness of the DRM viruses was shown to be significantly lower than the wild type. Deep-sequencing analyses of NS3 protease inhibitor-treated HCV-infected patients suggest a limit of HCV viral load suppression of 3.6 to 3.8 log
10
with NS3 protease inhibitor monotherapy that does not suppress the identified preexisting NS3 DRMs and thus a need for a combination therapy.
Serratia marcescens Necrotizing Fasciitis Presenting as Bilateral Breast Necrosis
Authors: Rehman Tayyab , Moore Thomas A. , Seoane Leonardo
Published: July 2012

Serratia marcescens
is an extremely rare cause of necrotizing fasciitis. We report the first case of necrotizing fasciitis of the chest wall due to infection with
S. marcescens
that initially manifested as bilateral breast necrosis. The patient had a fulminant course leading to death within 72 h of presentation. Literature pertinent to
S. marcescens
-mediated necrotizing fasciitis is also reviewed.
Detection of New Methicillin-Resistant Staphylococcus aureus Strains That Carry a Novel Genetic Homologue and Important Virulence Determinants
Authors: Sabat Artur J. , Koksal Mahir , Akkerboom Viktoria , Monecke Stefan , Kriegeskorte André , Hendrix Ron , Ehricht Ralf , Köck Robin , Becker Karsten , Friedrich Alexander W.
Published: July 2012

In this study, 18 methicillin-resistant
Staphylococcus aureus
(MRSA) isolates harboring staphylococcal cassette chromosome
mec
(SCC
mec
) type XI, recovered in the Dutch-German Euregio, were characterized by DNA microarrays. In contrast to previous data, we found two MRSA strains of different clonal lineages possessing SCC
mec
XI that carried important virulence determinants. The worrisome emergence of such toxigenic MRSA strains raises concerns that MRSA strains with enhanced virulence potential and impaired detectability by standard molecular assays may spread in Europe.
Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus Isolates from Patients Newly Identified as Nasal Carriers
Authors: Weir Susan K. , Fram Julia , Berg Gretchen , Kabbani Dima , Strymish Judith , Tang Melody , Fitzsimmons Dianne , Brecher Stephen M. , Gupta Kalpana
Published: July 2012

We aimed to determine whether additional molecular and microbiological evaluations of methicillin-resistant
Staphylococcus aureus
(MRSA) isolated from patients newly identified as nasal carriers were useful for control strategies and whether longitudinal testing during the same or repeat hospitalization changed MRSA status. Nasal swabs from patients positive by Xpert MRSA PCR and not known to be colonized in the previous year were cultured for
S. aureus
. Isolates were tested for resistance to a variety of antibiotics, including high-level mupirocin resistance (HLMR) and low-level mupirocin resistance (LLMR) and the presence of genes
mecA
and
mupA
and those for Panton-Valentine leukocidin (PVL), USA300, and USA400. Repeat nasal screens during the 6-month study were tested for continued presence of MRSA. Among 130 patients, cultures revealed MRSA in 85 (65.4%), methicillin-susceptible
S. aureus
in 19 (14.6%), and no growth in 26 (20%). MRSA isolates were USA300 positive in 13/85 (15.3%) and LLMR in 8/85 (9.4%) patients. No isolates were HLMR or
mupA
positive.
mecA
dropout was detected in 9/130 (6.9%) patients. The rate of subsequent MRSA infections in USA300-positive versus -negative patients was not different. MRSA nasal status remained concordant in 69/70 (98.6%) patients who had follow-up testing. The findings do not support expanding MRSA surveillance to include routine detection of genes for USA300, PVL, or
mupA
, all of which were either of low frequency or not significantly associated with MRSA infection risk in our population of newly identified nasal carriers. Repeat nasal screening for MRSA during the same or subsequent hospitalizations over 6 months could also be deferred, reducing costs associated with screening.
Probability of Negative Mycobacterium tuberculosis Complex Cultures Based on Time to Detection of Positive Cultures: a Multicenter Evaluation of Commercial-Broth-Based Culture Systems
Authors: Tyrrell Frances C. , Budnick Gary E. , Elliott Thor , Gillim-Ross Laura , Hildred Mary V. , Mahlmeister Peggy , Parrish Nicole , Pentella Michael , Vanneste Jolene , Wang Yun F. (Wayne) , Starks Angela M.
Published: July 2012

We conducted a multicenter study to determine whether
Mycobacterium tuberculosis
complex (MTBC) cultures in automated broth-based systems could reliably be considered negative sooner than 6 weeks. Laboratory sites used Bactec MGIT or BacT/Alert and tracked results of time to detection of all mycobacteria (TTD-all,
n
= 1547) and of MTBC (TTD-MTBC,
n
= 466) over 6-month periods from primarily (93%) respiratory specimens. Cumulative percentages by day detected and median TTD of initial and follow-up specimens were analyzed. The median TTD-MTBC for MGIT (
n
= 6 sites) was 14 days. For laboratories using standard processing procedures, 100% of MTBC were detected from initial and follow-up specimens in 28 and 35 days, respectively, and no yield of MTBC on solid or MGIT liquid media was observed after 5 weeks. The median TTD-MTBC for BacT/Alert (
n
= 3 sites) was 18 days, with 95% and 100% detected within 37 and 42 days, respectively. Analysis of TTD of positive MTBC cultures in broth can predict the probability of culture negativity at defined time points. Receipt of interim negative reports earlier than 6 weeks could assist clinicians in considering alternative diagnoses and could alter the timing and prioritization of public health interventions. Laboratories should analyze their own TTD data to inform protocol decisions. Laboratories using MGIT could issue reports of no growth of MTBC on initial specimens as early as 4 weeks and for patients undergoing treatment as early as 5 weeks postinoculation.
Modeling Uncertainty in Single-Copy Assays for HIV
Authors: Luo Rutao , Piovoso Michael J. , Zurakowski Ryan
Published: July 2012

We present a simple computational model of measurement accuracy for single-copy sensitivity assays (SCA) of HIV RNA that was developed from first principles. The model shows that the SCA is significantly right-skewed. Measured virus concentrations of 1 and 10 virions/ml had overlapping 95% confidence intervals and were statistically indistinguishable.
Microbial Dysbiosis in Pediatric Patients with Crohn's Disease
Authors: Kaakoush Nadeem O. , Day Andrew S. , Huinao Karina D. , Leach Steven T. , Lemberg Daniel A. , Dowd Scot E. , Mitchell Hazel M.
Published: July 2012

Microbial dysbiosis has been suggested to be involved in the pathogenesis of Crohn's disease (CD); however, many studies of gut microbial communities have been confounded by environmental and patient-related factors. In this study, the microbial flora of fecal samples from 19 children newly diagnosed with CD and 21 age-matched controls were analyzed using high-throughput sequencing to determine differences in the microbial composition between CD patients and controls. Analysis of the microbial composition of specific bacterial groups revealed that
Firmicutes
percentages were significantly lower in CD patients than in controls and that this was due largely to changes in the class
Clostridia. Bacteroidetes
and
Proteobacteria
percentages were higher and significantly higher in CD patients than in controls, respectively. Both the detection frequencies of
Bacteroidetes
and
Firmicutes
correlated (positively and negatively, respectively) with the calculated pediatric Crohn's disease activity index scores of patients. Upon further analysis, differences in the microbial compositions of patients with mild disease and moderate to severe disease were identified. Our findings indicate that a combination of different bacterial species or a dynamic interplay between individual species is important for disease and is consistent with the dysbiosis hypothesis of CD.
Quantitative Genomic and Antigenomic Enterovirus RNA Detection in Explanted Heart Tissue Samples from Patients with End-Stage Idiopathic Dilated Cardiomyopathy
Authors: Lévêque Nicolas , Renois Fanny , Talmud Déborah , Nguyen Yohan , Lesaffre François , Boulagnon Camille , Bruneval Patrick , Fornes Paul , Andréoletti Laurent
Published: July 2012

Standardized one-step real-time RT-PCR assay detected enterovirus RNA in cardiac biopsy samples from 4 of 20 patients suffering from idiopathic dilated cardiomyopathy (IDCM). The median viral load was 287 copies per microgram of total extracted nucleic acids, with positive- to negative-strand RNA ratios ranging from 2 to 20. These results demonstrate enterovirus persistence in the heart of IDCM patients, characterized by low viral loads and low positive- to negative-RNA ratios.
LGP2 Downregulates Interferon Production during Infection with Seasonal Human Influenza A Viruses That Activate Interferon Regulatory Factor 3
Authors: Malur Meghana , Gale Michael , Krug Robert M.
Published: July 2012

LGP2, a member of the RIG-I-like receptor family, lacks the amino-terminal caspase activation recruitment domains (CARDs) required for initiating the activation of interferon regulatory factor 3 (IRF3) and interferon (IFN) transcription. The role of LGP2 in virus infection is controversial, and the only LGP2 experiments previously carried out with mammalian influenza A viruses employed an attenuated, mouse-adapted H1N1 A/PR/8/34 (PR8) virus that does not encode the NS1 protein. Here we determine whether LGP2 has a role during infection with wild-type, nonattenuated influenza A viruses that have circulated in the human population, specifically two types of seasonal influenza A viruses: (i) H3N2 and H1N1 viruses that activate IRF3 and IFN transcription and (ii) recent H1N1 viruses that block these two activations. In human cells infected with an H3N2 virus that activates IRF3, overexpression of LGP2 or its repressor domain decreased STAT1 activation and IFN-β transcription approximately 10-fold. Overexpression of LGP2 also caused a 10-fold decrease of STAT1 activation during infection with other seasonal influenza A viruses that activate IRF3. Using LGP2
+/+
and LGP2
−/−
mouse cells, we show that endogenous LGP2 decreased IFN production during H3N2 virus infection 3- to 4-fold. In contrast, in both mouse and human cells infected with H1N1 viruses that do not activate IRF3, LGP2 had no detectable role. These results demonstrate that LGP2 downregulates IFN production during infection by seasonal influenza A viruses that activate IRF3 and IFN transcription. It is intriguing that LGP2, a host protein induced during influenza A virus infection, downregulates the host antiviral IFN response.
Tick-Borne Nyamanini Virus Replicates in the Nucleus and Exhibits Unusual Genome and Matrix Protein Properties
Authors: Herrel Marieke , Hoefs Nadja , Staeheli Peter , Schneider Urs
Published: July 2012

Tick-borne Nyamanini virus (NYMV) is the prototypic member of a recently discovered genus in the order
Mononegavirales
, designated
Nyavirus
. The NYMV genome codes for six distinct genes. Sequence similarity and structural properties suggest that genes 1, 5, and 6 encode the nucleoprotein (N), the glycoprotein (G), and the viral polymerase (L), respectively. The function of the other viral genes has been unknown to date. We found that the third NYMV gene codes for a protein which, when coexpressed with N and L, can reconstitute viral polymerase activity, suggesting that it represents a polymerase cofactor. The second viral gene codes for a small protein that inhibits viral polymerase activity and further strongly enhances the formation of virus-like particles when coexpressed with gene 4 and the viral glycoprotein G. This suggests that two distinct proteins serve a matrix protein function in NYMV as previously described for members of the family
Filoviridae
. We further found that NYMV replicates in the nucleus of infected cells like members of the family
Bornaviridae
. NYMV is a poor inducer of beta interferon, presumably because the viral genome is 5′ monophosphorylated and has a protruding 3′ terminus as observed for bornaviruses. Taken together, our results demonstrate that NYMV possesses biological properties previously regarded as typical for filoviruses and bornaviruses, respectively.
Myd88-Dependent Toll-Like Receptor 7 Signaling Mediates Protection from Severe Ross River Virus-Induced Disease in Mice
Authors: Neighbours Lauren M. , Long Kristin , Whitmore Alan C. , Heise Mark T.
Published: July 2012

Arthralgia-associated alphaviruses, including chikungunya virus (CHIKV) and Ross River virus (RRV), pose significant public health threats because of their ability to cause explosive outbreaks of debilitating arthralgia and myalgia in human populations. Although the host inflammatory response is known to contribute to the pathogenesis of alphavirus-induced arthritis and myositis, the role that Toll-like receptors (TLRs), which are major regulators of host antiviral and inflammatory responses, play in the pathogenesis of alphavirus-induced arthritis and myositis has not been extensively studied. Using a mouse model of RRV-induced myositis/arthritis, we found that myeloid differentiation primary response gene 88 (Myd88)-dependent TLR7 signaling is involved in protection from severe RRV-associated disease. Infections of Myd88- and TLR7-deficient mouse strains with RRV revealed that both Myd88 and TLR7 significantly contributed to protection from RRV-induced mortality, and both mouse strains exhibited more severe tissue damage than wild-type (WT) mice following RRV infection. While viral loads were unchanged in either Myd88 or TLR7 knockout mice compared to WT mice at early times postinfection, both Myd88 and TLR7 knockout mice exhibited higher viral loads than WT mice at late times postinfection. Furthermore, while high levels of RRV-specific antibody were produced in TLR7-deficient mice, this antibody had very little neutralizing activity and had lower affinity than WT antibody. Additionally, TLR7- and Myd88-deficient mice showed defects in germinal center activity, suggesting that TLR7-dependent signaling is critical for the development of protective antibody responses against RRV.
Site-Specific Cleavage of the Host Poly(A) Binding Protein by the Encephalomyocarditis Virus 3C Proteinase Stimulates Viral Replication
Authors: Kobayashi Mariko , Arias Carolina , Garabedian Alexandra , Palmenberg Ann C. , Mohr Ian
Published: July 2012

Although picornavirus RNA genomes contain a 3′-terminal poly(A) tract that is critical for their replication, the impact of encephalomyocarditis virus (EMCV) infection on the host poly(A)-binding protein (PABP) remains unknown. Here, we establish that EMCV infection stimulates site-specific PABP proteolysis, resulting in accumulation of a 45-kDa N-terminal PABP fragment in virus-infected cells. Expression of a functional EMCV 3C proteinase was necessary and sufficient to stimulate PABP cleavage in uninfected cells, and bacterially expressed 3C cleaved recombinant PABP
in vitro
in the absence of any virus-encoded or eukaryotic cellular cofactors. N-terminal sequencing of the resulting C-terminal PABP fragment identified a 3C
pro
cleavage site on PABP between amino acids Q437 and G438, severing the C-terminal protein-interacting domain from the N-terminal RNA binding fragment. Single amino acid substitution mutants with changes at Q437 were resistant to 3C
pro
cleavage
in vitro
and
in vivo
, validating that this is the sole detectable PABP cleavage site. Finally, while ongoing protein synthesis was not detectably altered in EMCV-infected cells expressing a cleavage-resistant PABP variant, viral RNA synthesis and infectious virus production were both reduced. Together, these results establish that the EMCV 3C proteinase mediates site-specific PABP cleavage and demonstrate that PABP cleavage by 3C regulates EMCV replication.
TLR7 Recognition Is Dispensable for Influenza Virus A Infection but Important for the Induction of Hemagglutinin-Specific Antibodies in Response to the 2009 Pandemic Split Vaccine in Mice
Authors: Jeisy-Scott Victoria , Kim Jin Hyang , Davis William G. , Cao Weiping , Katz Jacqueline M. , Sambhara Suryaprakash
Published: July 2012

Recognition of pathogen-associated molecular patterns by pattern recognition receptors of the innate immune system is crucial for the initiation of innate and adaptive responses and for immunological memory. We investigated the role of TLR7 in the induction of adaptive immunity and long-term memory following influenza virus infection and vaccination in C57BL/6 mice. During infection with influenza A/PR8/34 virus, the absence of either TLR7 or MyD88 leads to reduced virus-specific antibodies in the serum and antibody-secreting cells in their secondary lymphoid organs, particularly in bone marrow. In spite of this, the absence of TLR7/MyD88 signaling did not impair the production of protective antibodies. Following immunization with the 2009 pandemic inactivated split vaccine, TLR7
−/−
mice had significantly lower levels of germinal center formation, antibody-secreting cells, and circulating influenza virus-specific antibodies than control animals. Consequently, TLR7
−/−
mice failed to develop protective immunological memory upon challenge. Furthermore, the immunogenicity of the split vaccine was likely due to TLR7 recognition of virion RNA, as its removal from the split vaccine significantly reduced the levels of influenza virus-specific antibodies and compromised the vaccine protective efficacy in mice. Taken together, our data demonstrate that TLR7 plays an important role in vaccine-induced humoral immune responses to influenza virus through the interaction with viral RNA present in the split vaccine.
The Secreted G Protein of Human Respiratory Syncytial Virus Antagonizes Antibody-Mediated Restriction of Replication Involving Macrophages and Complement
Authors: Bukreyev Alexander , Yang Lijuan , Collins Peter L.
Published: July 2012

The respiratory syncytial virus (RSV) G and F glycoproteins are the neutralization antigens, and G also is expressed in a soluble form (sG). Previously, sG was demonstrated to reduce the efficiency of RSV antibody-mediated neutralization by serving as an antigen decoy and to inhibit the antibody-mediated antiviral effects of Fc receptor-bearing leukocytes. The present study demonstrated that effective antibody-mediated restriction
in vivo
, and the evasion of this restriction by sG, involves pulmonary macrophages and complement, but not neutrophils.
Reovirus Replication Protein μ2 Influences Cell Tropism by Promoting Particle Assembly within Viral Inclusions
Authors: Ooms Laura S. , Jerome W. Gray , Dermody Terence S. , Chappell James D.
Published: July 2012

The double-stranded RNA virus mammalian reovirus displays broad cell, tissue, and host tropism. A critical checkpoint in the reovirus replication cycle resides within viral cytoplasmic inclusions, which are biosynthetic centers of genome multiplication and new-particle assembly. Replication of strain type 3 Dearing (T3) is arrested in Madin-Darby canine kidney (MDCK) cells at a step subsequent to inclusion development and prior to formation of genomic double-stranded RNA. This phenotype is primarily regulated by viral replication protein μ2. To understand how reovirus inclusions differ in productively and abortively infected MDCK cells, we used confocal immunofluorescence and thin-section transmission electron microscopy (TEM) to probe inclusion organization and particle morphogenesis. Although no abnormalities in inclusion morphology or viral protein localization were observed in T3-infected MDCK cells using confocal microscopy, TEM revealed markedly diminished production of mature progeny virions. T3 inclusions were less frequent and smaller than those formed by T3-T1M1, a productively replicating reovirus strain, and contained decreased numbers of complete particles. T3 replication was enhanced when cells were cultivated at 31°C, and inclusion ultrastructure at low-temperature infection more closely resembled that of a productive infection. These results indicate that particle assembly in T3-infected MDCK cells is defective, possibly due to a temperature-sensitive structural or functional property of μ2. Thus, reovirus cell tropism can be governed by interactions between viral replication proteins and the unique cell environment that modulate efficiency of particle assembly.
Evidence For Multiple Cell Death Pathways during Development of Experimental Cytomegalovirus Retinitis in Mice with Retrovirus-Induced Immunosuppression: Apoptosis, Necroptosis, and Pyroptosis
Authors: Chien Hsin , Dix Richard D.
Published: July 2012

AIDS-related human cytomegalovirus (HCMV) retinitis remains a major ophthalmologic problem worldwide. Although this sight-threatening disease is well characterized clinically, many pathogenic issues remain unresolved, among them a basic understanding of the relative roles of cell death pathways during development of retinal tissue destruction. Using an established model of experimental murine cytomegalovirus (MCMV) retinitis in mice with retrovirus-induced immunosuppression (MAIDS), we initially investigated MCMV-infected eyes for evidence of apoptosis-associated molecules in mice with MAIDS of 4 weeks' (MAIDS-4) and 10 weeks' (MAIDS-10) duration, which were resistant and susceptible to retinal disease, respectively, but which harbored equivalent amounts of infectious MCMV. Whereas MCMV-infected eyes of MAIDS-4 mice showed little evidence of apoptosis-associated molecules, MCMV-infected eyes of MAIDS-10 mice showed significant amounts of tumor necrosis factor alpha (TNF-α), TNF receptors 1 and 2, active caspase 8, active caspase 3, TNF-related apoptosis-inducing ligand (TRAIL), TRAIL-R(DR5), Fas, and Fas ligand mRNAs and/or proteins, all detected at peak amounts prior to development of most severe retinal disease. Immunohistochemical staining showed macrophages, granulocytes (neutrophils), Müller cells, and microglial cells as TNF-α sources. Remarkably, quantification of apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay suggested that apoptosis contributed minimally to retinal disease in MCMV-infected eyes of MAIDS-10 mice. Subsequent studies demonstrated that MCMV-infected eyes of MAIDS-10 mice, but not MAIDS-4 mice, showed evidence of significant increases in molecules associated with two additional cell death pathways, necroptosis (receptor-interacting protein 1 [RIP1] and RIP3 mRNAs) and pyroptosis (caspase 1, interleukin 1β [IL-1β], and IL-18 mRNAs). We conclude that apoptosis, necroptosis, and pyroptosis participate simultaneously during MAIDS-related MCMV retinitis, and all may play a role during AIDS-related HCMV retinitis.
Control of Early Theiler's Murine Encephalomyelitis Virus Replication in Macrophages by Interleukin-6 Occurs in Conjunction with STAT1 Activation and Nitric Oxide Production
Authors: Moore Tyler C. , Bush Katherine L. , Cody Liz , Brown Deborah M. , Petro Thomas M.
Published: July 2012

During Theiler's murine encephalomyelitis virus (TMEV) infection of macrophages, it is thought that high interleukin-6 (IL-6) levels contribute to the demyelinating disease found in chronically infected SJL/J mice but absent in B10.S mice capable of clearing the infection. Therefore, IL-6 expression was measured in TMEV-susceptible SJL/J and TMEV-resistant B10.S macrophages during their infection with TMEV DA strain or responses to lipopolysaccharide (LPS) or poly(I · C). Unexpectedly, IL-6 production was greater in B10.S macrophages than SJL/J macrophages during the first 24 h after stimulation with TMEV, LPS, or poly(I · C). Further experiments showed that in B10.S, SJL/J, and RAW264.7 macrophage cells, IL-6 expression was dependent on extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) and enhanced by exogenous IL-12. In SJL/J and RAW264.7 macrophages, exogenous IL-6 resulted in decreased TMEV replication, earlier activation of STAT1 and STAT3, production of nitric oxide, and earlier upregulation of several antiviral genes downstream of STAT1. However, neither inhibition of IL-6-induced nitric oxide nor knockdown of STAT1 diminished the early antiviral effect of exogenous IL-6. In addition, neutralization of endogenous IL-6 from SJL/J macrophages with Fab antibodies did not exacerbate early TMEV infection. Therefore, endogenous IL-6 expression after TMEV infection is dependent on ERK MAPK, enhanced by IL-12, but too slow to decrease viral replication during early infection. In contrast, exogenous IL-6 enhances macrophage control of TMEV infection through preemptive antiviral nitric oxide production and antiviral STAT1 activation. These results indicate that immediate-early production of IL-6 could protect macrophages from TMEV infection.
A Combination of Broadly Neutralizing HIV-1 Monoclonal Antibodies Targeting Distinct Epitopes Effectively Neutralizes Variants Found in Early Infection
Authors: Goo Leslie , Jalalian-Lechak Zahra , Richardson Barbra A. , Overbaugh Julie
Published: July 2012

Neutralizing antibody protection against HIV-1 may require broad and potent antibodies targeting multiple epitopes. We tested 7 monoclonal antibodies (MAbs) against 45 viruses of diverse subtypes from early infection. The CD4 binding site MAb NIH45-46W was most broad and potent (91% coverage; geometric mean 50% inhibitory concentration [IC
50
], 0.09 μg/ml). Combining NIH45-46W and a V3-specific MAb, PGT128, neutralized 96% of viruses, while PGT121, another V3-specific MAb, neutralized the remainder. Thus, 2 or 3 antibody specificities may prevent infection by most HIV-1 variants.
Hepatitis C Virus-Induced Autophagy Is Independent of the Unfolded Protein Response
Authors: Mohl Bjorn-Patrick , Tedbury Philip R. , Griffin Stephen , Harris Mark
Published: July 2012

Hepatitis C virus (HCV) has been shown to induce autophagy and the unfolded protein response (UPR), but the mechanistic link between the induction of these two cellular processes remains unclear. We demonstrate here that HCV infection induces autophagy, as judged by accumulation of lipidated LC3-II, and that this induction occurs rapidly after infection, preceding the stimulation of the UPR, which occurs only at later stages, after the viral envelope glycoproteins have been expressed to high levels. Furthermore, both genotype 1b and 2a subgenomic replicons expressing nonstructural (NS3-5B) proteins and JFH-1 virus lacking the envelope glycoproteins potently induced autophagy in the absence of detectable UPR. This ability was also shared by a subgenomic replicon derived from the related GB virus B (GBV-B). We also show that small interfering RNA (siRNA)-mediated silencing of the key UPR inducer, Ire1, has no effect on HCV genome replication or the induction of autophagy, further demonstrating that the UPR is not required for these processes. Lastly, we demonstrate that the HCV replicase does not colocalize with autophagosomes, suggesting that the induction of autophagy is not required to generate the membrane platform for HCV RNA replication.
The H275Y Neuraminidase Mutation of the Pandemic A/H1N1 Influenza Virus Lengthens the Eclipse Phase and Reduces Viral Output of Infected Cells, Potentially Compromising Fitness in Ferrets
Authors: Pinilla Lady Tatiana , Holder Benjamin P. , Abed Yacine , Boivin Guy , Beauchemin Catherine A. A.
Published: July 2012

The H275Y amino acid substitution of the neuraminidase gene is the most common mutation conferring oseltamivir resistance in the N1 subtype of the influenza virus. Using a mathematical model to analyze a set ofin vitroexperiments that allow for the full characterization of the viral replication cycle, we show that the primary effects of the H275Y substitution on the pandemic H1N1 (H1N1pdm09) strain are to lengthen the mean eclipse phase of infected cells (from 6.6 to 9.1 h) and decrease (by 7-fold) the viral burst size, i.e., the total number of virions produced per cell. We also find, however, that the infectious-unit-to-particle ratio of the H275Y mutant strain is 12-fold higher than that of the oseltamivir-susceptible strain (0.19 versus 0.016 per RNA copy). A parallel analysis of the H275Y mutation in the prior seasonal A/Brisbane/59/2007 background shows similar changes in the infection kinetic parameters, but in this background, the H275Y mutation also allows the mutant to infect cells five times more rapidly. Competitive mixed-strain infectionsin vitro, where the susceptible and resistant H1N1pdm09 strains must compete for cells, are characterized by higher viral production by the susceptible strain but suggest equivalent fractions of infected cells in the culture. In ferrets, however, the mutant strain appears to suffer a delay in its infection of the respiratory tract that allows the susceptible strain to dominate mixed-strain infections.
NEW TREATMENT OF THE NONCOMMUTATIVE DIRAC EQUATION WITH A COULOMB POTENTIAL
Authors: KHODJA LAMINE , ZAIM SLIMANE
Published: July 2012

Using the approach of the modified Euler–Lagrange field equation together with the corresponding Seiberg–Witten maps of the dynamical fields, a noncommutative Dirac equation with a Coulomb potential is derived. We then find the noncommutative modification to the energy levels and the possible new transitions. In the nonrelativistic limit a general form of the Hamiltonian of the hydrogen atom is obtained, and we show that the noncommutativity plays the role of spin and magnetic field which gives the hyperfine structure.
HIGH ENERGY NEUTRINO OSCILLATION AT THE PRESENCE OF THE LORENTZ INVARIANCE VIOLATION
Authors: MOTIE IMAN , XUE SHE-SHENG
Published: July 2012

Due to quantum gravity fluctuations at the Planck scale, the space–time manifold is no longer continuous, but discretized. As a result the Lorentz symmetry is broken at very high energies. In this paper, we study the neutrino oscillation pattern due to the Lorentz invariance violation (LIV), and compare it with the normal neutrino oscillation pattern due to neutrino masses. We find that at very high energies, neutrino oscillation pattern is very different from the normal one. This could provide an possibility to study the Lorentz invariance violation by measuring the oscillation pattern of very high energy neutrinos from a cosmological distance.
INTERSECTION OF YANG–MILLS THEORY WITH GAUGE DESCRIPTION OF GENERAL RELATIVITY
Authors: KOBER MARTIN
Published: July 2012

An intersection of Yang–Mills theory with the gauge description of general relativity is considered. This intersection has its origin in a generalized algebra, where the generators of the SO(3, 1) group as gauge group of general relativity and the generators of a SU(N) group as gauge group of Yang–Mills theory are not separated anymore but are related by fulfilling nontrivial commutation relations with each other. Because of the Coleman–Mandula theorem this algebra cannot be postulated as Lie algebra. As consequence, extended gauge transformations as well as an extended expression for the field strength tensor is obtained, which contains a term consisting of products of the Yang–Mills connection and the connection of general relativity. Accordingly a new gauge invariant action incorporating the additional term of the generalized field strength tensor is built, which depends of course on the corresponding tensor determining the additional intersection commutation relations. This means that the theory describes a decisively modified interaction structure between the Yang–Mills gauge field and the gravitational field leading to a violation of the equivalence principle.
GREEN FUNCTIONS IN LORENTZ INVARIANT NONCOMMUTATIVE SPACE–TIME
Authors: ABREU EVERTON M. C. , NEVES MARIO J.
Published: July 2012

In this paper we investigated the causality problem present in the recent published work about the Doplicher–Fredenhagen–Roberts–Amorim (DFRA) noncommutative framework which analyzed the complex scalar field. We described the noncommutative Klein–Gordon equation with a source term. Its solution was accomplished through the retarded, advanced and causal Green functions constructed in this noncommutative ten-dimensional DFRA space–time. We believe that this solution constitutes the first step in the elaboration of a quantum field theory using the DFRA formalism where the well known noncommutative parameter from now on is an ordinary coordinate of the system and therefore has a canonical conjugate momentum. We discussed the dimensional reduction of this noncommutative space–time (D = 10) in order to recover commutativity in D = 4 space–time, which is not the usual one in noncommutativity literature.
QUANTUM HALL EDGE PHYSICS AND ITS ONE-DIMENSIONAL LUTTINGER LIQUID DESCRIPTION
Authors: CIFTJA ORION
Published: July 2012

We describe the relationship between quantum Hall edge states and the one-dimensional Luttinger liquid model. The Luttinger liquid model originated from studies of one-dimensional Fermi systems, however, it results that many ideas inspired by such a model can find applications to phenomena occurring even in higher dimensions. Quantum Hall systems which essentially are correlated two-dimensional electronic systems in a strong perpendicular magnetic field have an edge. It turns out that the quantum Hall edge states can be described by a one-dimensional Luttinger model. In this work, we give a general background of the quantum Hall and Luttinger liquid physics and then point out the relationship between the quantum Hall edge states and its one-dimensional Luttinger liquid representation. Such a description is very useful given that the Luttinger liquid model has the property that it can be bosonized and solved. The fact that we can introduce a simpler model of noninteracting bosons, even if the quantum Hall edge states of electrons are interacting, allows one to calculate exactly various quantities of interest. One such quantity is the correlation function which, in the asymptotic limit, is predicted to have a power law form. The Luttinger liquid model also suggests that such a power law exponent should have a universal value. A large number of experiments have found the quantum Hall edge states to show behavior consistent with a Luttinger liquid description. However, while a power law dependence of the correlation function has been observed, the experimental values of the exponent appear not to be universal. This discrepancy might be due to various correlation effects between electrons that sometimes are not easy to incorporate within a standard Luttinger liquid model.
A LUTTINGER LIQUID CORE INSIDE HELIUM-4 FILLED NANOPORES
Authors: DEL MAESTRO ADRIAN
Published: July 2012

As helium-4 is cooled below 2.17 K it undergoes a phase transition to a fundamentally quantum mechanical state of matter known as a superfluid which supports flow without viscosity. This type of dissipationless transport can be observed by forcing helium to travel through a narrow constriction that the normal liquid could not penetrate. Recent experiments have highlighted the feasibility of fabricating smooth pores with nanometer radii, that approach the truly one-dimensional limit where it is believed that a system of bosons (like helium-4) may have startlingly different behavior than in three dimensions. The one-dimensional system is predicted to have a linear hydrodynamic description known as Luttinger liquid (LL) theory, where no type of long range order can be sustained. In the limit where the pore radius is small, LL theory would predict that helium inside the channel behaves as a sort of quasi-supersolid with all correlations decaying as power-law functions of distance at zero temperature. We have performed large scale quantum Monte Carlo simulations of helium-4 inside nanopores of varying radii at low temperature with realistic helium–helium and helium-pore interactions. The results indicate that helium inside the nanopore forms concentric cylindrical shells surrounding a core that can be described via LL theory and provides insights into the exciting possibility of the experimental detection of this intriguing low-dimensional state of matter.
SOME EXPERIMENTAL TESTS OF TOMONAGA–LUTTINGER LIQUIDS
Authors: GIAMARCHI T.
Published: July 2012

The Tomonaga–Luttinger–Liquid (TLL) has been the cornerstone of our understanding of the properties of one dimensional systems. This universal set of properties plays in one dimension, the same role than Fermi liquid plays for the higher dimensional metals. I will give in these notes an overview of some of the experimental tests that were made to probe such TLL physics. In particular I will detail some of the recent experiments that were made in spin systems and which provided remarkable quantitative tests of the TLL physics.
LUTTINGER MODEL AND LUTTINGER LIQUIDS
Authors: MASTROPIETRO VIERI
Published: July 2012

The Luttinger model owes its solvability to a number of peculiar features, like its linear relativistic dispersion relation, which are absent in more realistic fermionic systems. Nevertheless according to the Luttinger liquid conjecture a number of relations between exponents and other physical quantities, which are valid in the Luttinger model, are believed to be true in a wide class of systems, including tight binding or jellium one-dimensional fermionic systems. Recently a rigorous proof of several Luttinger liquid relations in nonsolvable models has been achieved; it is based on exact Renormalization Group methods coming from Constructive Quantum Field Theory and its main steps will be reviewed below.
AN EXPANDED LUTTINGER MODEL
Authors: MATTIS DANIEL C.
Published: July 2012

This paper generalizes Luttinger's model by introducing curvature (d2ε(k)/dk2≠0) into the kinetic energy. An exact solution for arbitrary interactions is still possible in principle, but it now requires disentangling the eigenvalue spectrum of an harmonic string of interacting boson fields at each value of q. The additional boson fields, extracted from the excitation spectrum of the Fermi sea, are self-selected according to the nature and strength of the dispersion.
LONG TIME CORRELATIONS OF NONLINEAR LUTTINGER LIQUIDS
Authors: PEREIRA RODRIGO G.
Published: July 2012

An overview is given of the limitations of Luttinger liquid theory in describing the real time equilibrium dynamics of critical one-dimensional systems with nonlinear dispersion relation. After exposing the singularities of perturbation theory in band curvature effects that break the Lorentz invariance of the Tomonaga–Luttinger model, the origin of high frequency oscillations in the long time behaviour of correlation functions is discussed. The notion that correlations decay exponentially at finite temperature is challenged by the effects of diffusion in the density–density correlation due to umklapp scattering in lattice models.
SYNTHESIS, MICROSTRUCTURAL AND MAGNETIC CHARACTERIZATIONS OF SELF-ASSEMBLED HEMATITE NANOPARTICLES
Authors: BHUSHAN BHAVYA , MUKHERJEE SAMRAT , DAS DIPANKAR
Published: July 2012

Phase pure hematite nanoparticles coated with octyl ether and oleic acid were synthesized by a facile chemical route. Nanoparticles in the size range 7–25 nm were obtained by annealing the as-prepared samples at different temperatures. Transmission electron micrographs revealed that the particles tend to organize themselves in chain-like structures consisting of three to six nanoparticles along a common axis. The reason behind this oriented attachment is traced to the exchange coupling between the nanoparticles. Effect of exchange coupling was also evidenced as suppression of superparamagnetism in lower dimension hematite nanoparticles. Morin transition was observed around 260 K by magnetization measurement for hematite nanoparticles having average crystallite size of 25 nm.
LOW TEMPERATURE NEUTRON DIFFRACTION ON CONGRUENT AND NEAR STOICHIOMETRIC LiNbO3
Authors: YAO SHUHUA , SANG YUANHUA , YU DEHONG , AVDEEV MAXIM , LIU HONG , WANG JIYANG , ZHANG NANA
Published: July 2012

Neutron powder diffraction has been carried out on a congruent LiNbO 3 sample containing 7 Li isotope ( C 7 LN ) and a near stoichiometric Mg doped LiNbO 3 sample ( Mg : NSLN ) in the temperature range of 4 K and 90 K. Large anisotropic displacement parameters (ADPs) of the Li ions have shown evidence of large disorder along the c-axis for both samples. The results have shown no evidence for the existence of anomalous structural behavior for both samples at low temperatures, although abnormal structural features at 55 K and 100 K for a LiNbO 3 crystal having different Li content as the samples used in the present studies have been observed by Fernandez-Ruiz et al. [Phys. Rev. B72 (2005) 184108].