bluuebunny/crossref_metadata_2025 huggingface dataset:
A General Mechanism for Network-Dosage Compensation in Gene Circuits
Authors: Acar Murat , Pando Bernardo F. , Arnold Frances H. , Elowitz Michael B. , van Oudenaarden Alexander
Published: September 2010

Invariant in the Face of Change

The number of copies of a gene network in a cell, or network dosage, is altered in a variety of situations, including switching between haploid and diploid states, and during cell cycle progression. Combining experimental and computational approaches,

Acar
et al.

(p.
1656
) explore how the activity of a gene network can be invariant despite alterations in network dosage. A two-component genetic circuit with elements of opposite regulatory activity (that is, an activator and an inhibitor) was revealed as a minimal requirement. Specific network topologies and a 1-to-1 interaction stoichiometry between the activating and inhibiting agents also represented essential elements for network-dosage compensation.
Alkali-Stabilized Pt-OH

x

Species Catalyze Low-Temperature Water-Gas Shift Reactions
Authors: Zhai Yanping , Pierre Danny , Si Rui , Deng Weiling , Ferrin Peter , Nilekar Anand U. , Peng Guowen , Herron Jeffrey A. , Bell David C. , Saltsburg Howard , Mavrikakis Manos , Flytzani-Stephanopoulos Maria
Published: September 2010

Substituting Salt for Cerium Oxide

The water-gas shift reaction converts carbon monoxide and water to hydrogen and carbon dioxide. Catalysts that operate at lower temperatures will be useful in fuel cells. Nanoparticles of platinum adsorbed on reducible oxides, such as ceria, can stabilize catalytically active Ptoxygen species.

Zhai
et al.

(p.
1633
) now show that, when alkali atoms are added, atomically dispersed Pt can be an active catalyst for the water-gas shift reaction at ∼100°C, even on simple oxides such as alumina and silica.
Genetic Restoration of the Florida Panther
Authors: Johnson Warren E. , Onorato David P. , Roelke Melody E. , Land E. Darrell , Cunningham Mark , Belden Robert C. , McBride Roy , Jansen Deborah , Lotz Mark , Shindle David , Howard JoGayle , Wildt David E. , Penfold Linda M. , Hostetler Jeffrey A. , Oli Madan K. , O’Brien Stephen J.
Published: September 2010

Return of the Florida Panther

The Florida panther is an endangered lineage that has been the target of extensive human management to maintain genetic diversity within a small population. Now,

Johnson
et al.

(p.
1641
; see the Perspective by

Packer

) provide comprehensive genetic and demographic analyses of a project to rescue the Florida panther from inbreeding, low genetic diversity, inbreeding depression, and demographic stochasticity by outcrossing it to Texas pumas. The genetics and reproductive fitness traits of different panther populations and their crosses reveal the benefits of outcrossing on survival, genetic diversity, male reproductive characteristics, and population demography.
Without Social Context?

The Evolution of Language
by W. Tecumseh Fitch

Cambridge University Press, Cambridge, 2010. 623 pp. $120, £70. ISBN 9780521859936. Paper, $55, £29.99. ISBN 9780521677363.
The Evolution of Human Language
Biolinguistic Perspectives

Richard K. Larson, Viviane Déprez, and Hiroko Yamakido, Eds.

Cambridge University Press, Cambridge, 2010. 279 pp. $105, £60. ISBN 9780521516457. Paper, $41, £23.99. ISBN 9780521736251.
Authors: Enfield N. J.
Published: September 2010

Both of these considerations of the evolution of language draw on research from a wide range of fields, although Enfield believes they do not pay sufficient attention to the dynamic context of human social behavior.
Exposing a DUX Tale
Authors: Mahadevan Mani S.
Published: September 2010

A DNA sequence stabilizes the expression of a gene that may affect muscle development and lead to muscular dystrophy.
More Supernova Surprises
Authors: Laming J. Martin
Published: September 2010

Spectroscopic observations of the supernova SN1987A are providing a new window into high-energy shock physics.
Genomics Researchers Upset by Rivals' Publicity
Authors: Pennisi Elizabeth
Published: September 2010

Last week, announcements by rival teams upstaged two current projects by Pennsylvania State University genomicist Stephan Schuster: the genome sequences of cacao and the Tasmanian devil.
Behind the Eco-Label, a Debate Over Antarctic Toothfish
Authors: Stokstad Erik
Published: September 2010

The controversial case of the Antarctic toothfish has raised questions about the gold standard for environmentally friendly fishing.
Enzyme-Linked Immunosorbent Assay for Detection of Filovirus Species-Specific Antibodies
Authors: Nakayama Eri , Yokoyama Ayaka , Miyamoto Hiroko , Igarashi Manabu , Kishida Noriko , Matsuno Keita , Marzi Andrea , Feldmann Heinz , Ito Kimihito , Saijo Masayuki , Takada Ayato
Published: September 2010

Several enzyme-linked immunosorbent assays (ELISAs) for the detection of filovirus-specific antibodies have been developed. However, diagnostic methods to distinguish antibodies specific to the respective species of filoviruses, which provide the basis for serological classification, are not readily available. We established an ELISA using His-tagged secreted forms of the transmembrane glycoproteins (GPs) of five different Ebola virus (EBOV) species and one Marburg virus (MARV) strain as antigens for the detection of filovirus species-specific antibodies. The GP-based ELISA was evaluated by testing antisera collected from mice immunized with virus-like particles as well as from humans and nonhuman primates infected with EBOV or MARV. In our ELISA, little cross-reactivity of IgG antibodies was observed in most of the mouse antisera. Although sera and plasma from some patients and monkeys showed notable cross-reactivity with the GPs from multiple filovirus species, the highest reactions of IgG were uniformly detected against the GP antigen homologous to the virus species that infected individuals. We further confirmed that MARV-specific IgM antibodies were specifically detected in specimens collected from patients during the acute phase of infection. These results demonstrate the usefulness of our ELISA for diagnostics as well as ecological and serosurvey studies.
Characterization of Pneumonia Due toStreptococcus equisubsp.zooepidemicusin Dogs
Authors: Priestnall Simon L. , Erles Kerstin , Brooks Harriet W. , Cardwell Jacqueline M. , Waller Andrew S. , Paillot Romain , Robinson Carl , Darby Alistair C. , Holden Matthew T. G. , Schöniger Sandra
Published: September 2010

Streptococcus equisubsp.zooepidemicushas been linked to cases of acute fatal pneumonia in dogs in several countries. Outbreaks can occur in kenneled dog populations and result in significant levels of morbidity and mortality. This highly contagious disease is characterized by the sudden onset of clinical signs, including pyrexia, dyspnea, and hemorrhagic nasal discharge. The pathogenesis ofS. equisubsp.zooepidemicusinfection in dogs is poorly understood. This study systematically characterized the histopathological changes in the lungs of 39 dogs from a large rehoming shelter in London, United Kingdom; the dogs were infected withS. equisubsp.zooepidemicus. An objective scoring system demonstrated thatS. equisubsp.zooepidemicuscaused pneumonia in 26/39 (66.7%) dogs, and most of these dogs (17/26 [65.4%]) were classified as severe fibrino-suppurative, necrotizing, and hemorrhagic. Three recently described superantigen genes (szeF,szeN, andszeP) were detected by PCR in 17/47 (36.2%) of theS. equisubsp.zooepidemicusisolates; however, there was no association between the presence of these genes and the histopathological score. The lungs ofS. equisubsp.zooepidemicus-infected dogs with severe respiratory signs and lung pathology did however have significantly higher mRNA levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 8 (IL-8) than in uninfected controls, suggesting a role for an exuberant host immune response in the pathogenesis of this disease.
Comparison of the
Babesia duncani
(WA1) IgG Detection Rates among Clinical Sera Submitted to a Reference Laboratory for WA1 IgG Testing and Blood Donor Specimens from Diverse Geographic Areas of the United States
Authors: Prince Harry E. , Lapé-Nixon Mary , Patel Hemlata , Yeh Cindy
Published: September 2010

All reported cases of WA1 babesiosis have occurred in the Pacific coast region of the United States, suggesting that WA1 is limited to this geographic area. However, we detected WA1 IgG in 27% of clinical sera sent to our laboratory for WA1 IgG testing from across the United States over a 2-year period, suggesting that exposure to WA1 or a closely related organism occurs outside Pacific coast states. We sought to determine if this high WA1 IgG detection rate among clinical specimens merely reflects WA1 seroprevalence outside the Pacific region. WA1 IgG, as well as
Babesia microti
IgG, was measured in 900 blood donor specimens from 9 states. Overall seroprevalence was 2.0% for WA1 and 0.4% for
B. microti
; regional seroprevalences ranged from 0 to 4% and 0 to 2%, respectively. Additional studies were performed to determine if WA1 IgG reactivity was attributable to polyclonal B-cell activation associated with acute Epstein-Barr virus (EBV) infection; 40 WA1 IgG-positive clinical sera and the 18 WA1 IgG-positive blood donor specimens were all negative for EBV capsid antigen (EBVCA) IgM (a marker of acute EBV infection), and 40 EBVCA IgM-positive sera were all negative for WA1 IgG. These findings indicate that the high WA1 IgG detection rate among clinical specimens does not simply reflect the national WA1 seroprevalence among blood donors or nonspecific reactivity due to acute EBV infection. Rather, the findings suggest that infection with WA1 or a related organism is more common than indicated by the literature and is not limited to Pacific coast states.
A Single, Engineered Protein Therapeutic Agent Neutralizes Exotoxins from BothStaphylococcus aureusandStreptococcus pyogenes
Authors: Wang Ningyan , Mattis Daiva M. , Sundberg Eric J. , Schlievert Patrick M. , Kranz David M.
Published: September 2010

Staphylococcus aureusandStreptococcus pyogenessecrete exotoxins that act as superantigens, proteins that cause hyperimmune reactions by binding the variable domain of the T-cell receptor beta chain (Vβ), leading to stimulation of a large fraction of the T-cell repertoire. To develop potential neutralizing agents, we engineered Vβ mutants with high affinity for the superantigens staphylococcal enterotoxin B (SEB), SEC3, and streptococcal pyrogenic exotoxin A (SpeA). Unexpectedly, the high-affinity Vβ mutants generated against SEB cross-reacted with SpeA to a greater extent than they did with SEC3, despite greater sequence similarity between SEB and SEC3. Likewise, the Vβ mutants generated against SpeA cross-reacted with SEB to a greater extent than with SEC3. The structural basis of the high affinity and cross-reactivity was examined by single-site mutational analyses. The cross-reactivity seems to involve only one or two toxin residues. Soluble forms of the cross-reactive Vβ regions neutralized both SEB and SpeAin vivo, suggesting structure-based strategies for generating high-affinity neutralizing agents that can cross-react with multiple exotoxins.
Nested PCR-Linked Capillary Electrophoresis and Single-Strand Conformation Polymorphisms for Detection of Macrolide-Resistant
Mycoplasma pneumoniae
in Beijing, China
Authors: Lin Changying , Li Shaoli , Sun Hongmei , Zhao Hanqing , Feng Yanling , Cao Ling , Yuan Yi , Zhang Ting
Published: September 2010

Mycoplasma pneumoniae
is usually susceptible to macrolides, but macrolide-resistant strains have been found frequently in recent years. Mutations in domain V of the 23S rRNA gene of
M. pneumoniae
interfere with the binding of macrolides to rRNA and mediate macrolide resistance. In this study, we developed a rapid and inexpensive method that combines nested PCR (nPCR), single-strand conformation polymorphisms (SSCPs), and capillary electrophoresis (CE) to detect macrolide-resistant mutants directly from throat swabs. nPCR was used to specifically amplify
M. pneumoniae
23S rRNA gene fragments containing mutations, and amplicons were analyzed by CE-SSCP for macrolide resistance mutations, with results confirmed by sequencing. From January to December 2009, 665 throat swabs were collected in Beijing, China, yielding 110 samples that tested positive for
M. pneumoniae
by nPCR and serological testing. We randomly selected 64 positive throat swabs for CE-SSCP analysis. The A2063G mutation was found in 57 samples, and a coexisting T2611C mutation was identified in 1 sample. An A2063T mutation was identified in 1 sample. The total mutation rate was 91%. All mutant samples identified by nPCR-CE-SSCP were sequenced. The nPCR-CE-SSCP method could identify macrolide-resistant mutants directly from clinical samples. This is the first report of an nPCR-CE-SSCP assay for the detection of dominant mutations that confer macrolide resistance on
M. pneumoniae
. This approach would allow clinicians to choose appropriate therapy rapidly and could be used as a screening method for genetic mutations related to antibiotic resistance.
Improved Detection of Five Major Gastrointestinal Pathogens by Use of a Molecular Screening Approach
Authors: de Boer Richard F. , Ott Alewijn , Kesztyüs Barbara , Kooistra-Smid Anna M. D.
Published: September 2010

The detection of bacterial and parasitic gastrointestinal pathogens through culture and microscopy is laborious and time-consuming. We evaluated a molecular screening approach (MSA) for the detection of five major enteric pathogens:
Salmonella enterica
,
Campylobacter jejuni
,
Giardia lamblia
, Shiga toxin-producing
Escherichia coli
(STEC), and
Shigella
spp./enteroinvasive
E. coli
(EIEC), for use in the daily practice of a clinical microbiology laboratory. The MSA consists of prescreening of stool specimens with two real-time multiplex PCR (mPCR) assays, which give results within a single working day, followed by guided culture/microscopy of the positive or mPCR-inhibited samples. In the present 2-year overview, 28,185 stool specimens were included. The MSA was applied to 13,974 stool samples (49.6%), whereas 14,211 samples were tested by conventional methods only (50.4%). The MSA significantly increased the total detection rate compared to that of conventional methods (19.2% versus 6.4%). The detection of all included pathogens, with the exception of
S. enterica
, significantly improved. MSA detection frequencies were as follows:
C. jejuni
, 8.1%;
G. lamblia
, 4.7%;
S. enterica
, 3.0%; STEC, 1.9%; and
Shigella
spp./EIEC, 1.4%. The guided culture/microscopy was positive in 76.8%, 58.1%, 88.9%, 16.8%, and 18.1% of mPCR-positive specimens, respectively. Of all mPCRs, only 1.8% was inhibited. Other findings were that detection of mixed infections was increased (0.9% versus 0.02%) and threshold cycle (

C
T

) values for MSA guided culture/microscopy-positive samples were significantly lower than those for guided culture/microscopy-negative samples. In conclusion, an MSA for detection of gastrointestinal pathogens resulted in markedly improved detection rates and a substantial decrease in time to reporting of (preliminary) results.
Rhino-Orbitocerebral Zygomycosis Caused by
Conidiobolus incongruus
in an Immunocompromised Patient in Germany
Authors: Wüppenhorst Nicole , Lee Mi-Kyung , Rappold Elfriede , Kayser Gian , Beckervordersandforth Jan , de With Katja , Serr Annerose
Published: September 2010

Mucorales
(subphylum
Mucoromycotina
) are well-known agents of invasive mucormycosis, whereas
Entomophthorales
(subphylum
Entomophthoromycotina
) are rarely encountered in human diseases in temperate zones. Here we report a fatal case of invasive rhino-orbitocerebral entomophthoramycosis caused by
Conidiobolus incongruus
in a 78-year-old woman with myelodysplastic syndrome.
Performance of Genotypic Algorithms for Predicting HIV-1 Tropism Measured against the Enhanced-Sensitivity Trofile Coreceptor Tropism Assay
Authors: Sánchez Victoria , Masiá Mar , Robledano Catalina , Padilla Sergio , Ramos José Manuel , Gutiérrez Félix
Published: September 2010

The objectives of this study were to assess the performance of genotypic algorithms for predicting CXCR4-using virus, with enhanced sensitivity Trofile HIV coreceptor tropism assay (ES Trofile) as the reference, and to compare the concordance/accuracy of genotypic tests with ES Trofile and with the original Trofile assay. Paired phenotypic and genotypic determinations of HIV-1 coreceptor usage were compared in plasma samples from HIV-1-infected patients. Sequencing of the third hypervariable (V3) loop of the viral gene and phenotypic assays were performed for each sample. Genotypic rules used to predict tropism were Geno2pheno (false-positive rate at 1 to 20%), position-specific scoring matrix X4R5 (PSSM
X4R5
) and PSSM
sinsi
(where “sinsi” stands for syncytium inducing and non-syncytium inducing), and the 11/25, 11/24/25, and net charge rules. Two hundred forty-four phenotypic and genotypic samples were tested. Coreceptor usage was obtained from ES Trofile for 145 (59%) samples and from Trofile for 99 (41%) samples. The highest concordance (82.6%) was obtained with PSSM
X4R5
when ES Trofile was used as the reference. Geno2pheno at a 20% false-positive rate showed the highest sensitivity (76.7%) for CXCR4-using virus detection with ES Trofile. Samples from naïve subjects and those with CD4 cell counts between 200 and 500 cells/mm
3
showed the best predictive performance. Overall, the accuracy of the bioinformatics tools to detect CXCR4-using virus was similar for ES Trofile and Trofile; however, the negative predictive values for genotypic tools with ES Trofile were slightly higher than they were with Trofile. The accuracy of genotypic algorithms for detecting CXCR4-using viruses is high when using ES Trofile as the reference. Results are similar to those obtained with Trofile. The concordance with ES Trofile is better with higher CD4 cell counts and nonexposure to antiretroviral therapy.
Evolution and Phylogeography of the Nonpathogenic Calicivirus RCV-A1 in Wild Rabbits in Australia
Authors: Jahnke Marlene , Holmes Edward C. , Kerr Peter J. , Wright John D. , Strive Tanja
Published: September 2010

Despite its potential importance for the biological control of European rabbits, relatively little is known about the evolution and molecular epidemiology of rabbit calicivirus Australia 1 (RCV-A1). To address this issue we undertook an extensive evolutionary analysis of 36 RCV-A1 samples collected from wild rabbit populations in southeast Australia between 2007 and 2009. Based on phylogenetic analysis of the entire capsid sequence, six clades of RCV-A1 were defined, each exhibiting strong population subdivision. Strikingly, our estimates of the time to the most recent common ancestor of RCV-A1 coincide with the introduction of rabbits to Australia in the mid-19th century. Subsequent divergence events visible in the RCV-A1 phylogenies likely reflect key moments in the history of the European rabbit in Australia, most notably the bottlenecks in rabbit populations induced by the two viral biocontrol agents used on the Australian continent, myxoma virus and rabbit hemorrhagic disease virus (RHDV). RCV-A1 strains therefore exhibit strong phylogeographic separation and may constitute a useful tool to study recent host population dynamics and migration patterns, which in turn could be used to monitor rabbit control in Australia.
Influenza A Virus Replication Induces Cell Cycle Arrest in G
0
/G
1
Phase
Authors: He Yuan , Xu Ke , Keiner Bjoern , Zhou Jianfang , Czudai Volker , Li Tianxian , Chen Ze , Liu Jinhua , Klenk Hans-Dieter , Shu Yue Long , Sun Bing
Published: September 2010

Many viruses interact with the host cell division cycle to favor their own growth. In this study, we examined the ability of influenza A virus to manipulate cell cycle progression. Our results show that influenza A virus A/WSN/33 (H1N1) replication results in G
0
/G
1
-phase accumulation of infected cells and that this accumulation is caused by the prevention of cell cycle entry from G
0
/G
1
phase into S phase. Consistent with the G
0
/G
1
-phase accumulation, the amount of hyperphosphorylated retinoblastoma protein, a necessary active form for cell cycle progression through late G
1
into S phase, decreased after infection with A/WSN/33 (H1N1) virus. In addition, other key molecules in the regulation of the cell cycle, such as p21, cyclin E, and cyclin D1, were also changed and showed a pattern of G
0
/G
1
-phase cell cycle arrest. It is interesting that increased viral protein expression and progeny virus production in cells synchronized in the G
0
/G
1
phase were observed compared to those in either unsynchronized cells or cells synchronized in the G
2
/M phase. G
0
/G
1
-phase cell cycle arrest is likely a common strategy, since the effect was also observed in other strains, such as H3N2, H9N2, PR8 H1N1, and pandemic swine H1N1 viruses. These findings, in all, suggest that influenza A virus may provide favorable conditions for viral protein accumulation and virus production by inducing a G
0
/G
1
-phase cell cycle arrest in infected cells.
BST-2 Diminishes HIV-1 Infectivity
Authors: Zhang Jianyong , Liang Chen
Published: September 2010

Bone marrow stromal cell antigen 2 (BST-2, also known as tetherin/CD317/HM1.24) inhibits the release of human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses by tethering virus particles to the cell surface. In this study, we provide evidence not only that the yield of cell-free HIV-1 particles is significantly reduced by BST-2 but also that the infectivity of these progeny virions is severely impaired. The lowered virion infectivity is due to the accumulation of pr55 Gag precursor and the p40Gag intermediates as well as to the loss of a mature core in the majority of HIV-1 particles. These data suggest that, in addition to impeding the release of HIV-1 particles from host cells, BST-2 may also interfere with the activation of viral protease and, as a result, impairs viral Gag processing as well as maturation of HIV-1 particles.
Cellular Immediate-Early Gene Expression Occurs Kinetically Upstream of Epstein-Barr Virus
bzlf1
and
brlf1
following Cross-Linking of the B Cell Antigen Receptor in the Akata Burkitt Lymphoma Cell Line
Authors: Ye Jianjiang , Gradoville Lyndle , Miller George
Published: September 2010

The Epstein-Barr virus (EBV) lytic activator genes
bzlf1
and
brlf1
are conventionally referred to as immediate-early (IE) genes. However, previous studies showed that the earliest expression of these genes was blocked by cycloheximide when the EBV lytic cycle was induced by histone deacetylase (HDAC) inhibitors and protein kinase C agonists. Anti-IgG activates a complex signal transduction pathway that leads to EBV lytic activation in the Akata cell line. Here we demonstrate that in Akata cells, where lytic cycle activation occurs very rapidly after anti-IgG treatment,
de novo
protein synthesis is also required for induction of
bzlf1
and
brlf1
expression. New protein synthesis is required up to 1.25 h after application of anti-IgG;
bzlf1
and
brlf1
mRNAs can be detected 1.5 h after anti-IgG. Five cellular IE genes were shown to be expressed by 1 h after addition of anti-IgG, and their expression preceded that of
bzlf1
and
brlf1
. These include early growth response genes (
egr1
,
egr2
, and
egr3
) and nuclear orphan receptors (
nr4a1
and
nr4a3
). These genes were activated by anti-IgG treatment of Akata cells with and without the EBV genome; therefore, their expression was not dependent on expression of any EBV gene product. EGR1, EGR2, and EGR3 proteins were kinetically upstream of ZEBRA and Rta proteins. Expression of EGR1, ZEBRA, and Rta proteins were inhibited by bisindolylmaleimide X, a selective inhibitor of PKC. The findings suggest a revised model in which the signal transduction cascade activated by cross-linking of the B cell receptor induces expression of cellular IE genes, such as early growth response and nuclear orphan receptor genes, whose products, in turn, regulate
bzlf1
and
brlf1
expression.
Coxsackievirus Infection Induces Autophagy-Like Vesicles and Megaphagosomes in Pancreatic Acinar Cells
In Vivo
Authors: Kemball Christopher C. , Alirezaei Mehrdad , Flynn Claudia T. , Wood Malcolm R. , Harkins Stephanie , Kiosses William B. , Whitton J. Lindsay
Published: September 2010

Autophagy can play an important part in protecting host cells during virus infection, and several viruses have developed strategies by which to evade or even exploit this homeostatic pathway. Tissue culture studies have shown that poliovirus, an enterovirus, modulates autophagy. Herein, we report on
in vivo
studies that evaluate the effects on autophagy of coxsackievirus B3 (CVB3). We show that in pancreatic acinar cells, CVB3 induces the formation of abundant small autophagy-like vesicles and permits amphisome formation. However, the virus markedly, albeit incompletely, limits the fusion of autophagosomes (and/or amphisomes) with lysosomes, and, perhaps as a result, very large autophagy-related structures are formed within infected cells; we term these structures megaphagosomes. Ultrastructural analyses confirmed that double-membraned autophagy-like vesicles were present in infected pancreatic tissue and that the megaphagosomes were related to the autophagy pathway; they also revealed a highly organized lattice, the individual components of which are of a size consistent with CVB RNA polymerase; we suggest that this may represent a coxsackievirus replication complex. Thus, these
in vivo
studies demonstrate that CVB3 infection dramatically modifies autophagy in infected pancreatic acinar cells.
Adenovirus E1B 55-Kilodalton Protein Is a p53-SUMO1 E3 Ligase That Represses p53 and Stimulates Its Nuclear Export through Interactions with Promyelocytic Leukemia Nuclear Bodies
Authors: Pennella Mario A. , Liu Yue , Woo Jennifer L. , Kim Chongwoo A. , Berk Arnold J.
Published: September 2010

Oncogenic transformation by adenovirus E1A and E1B-55K requires E1B-55K inhibition of p53 activity to prevent E1A-induced apoptosis. During viral infection, E1B-55K and E4orf6 substitute for the substrate-binding subunits of the host cell cullin 5 class of ubiquitin ligases, resulting in p53 polyubiquitinylation and proteasomal degradation. Here we show that E1B-55K alone also functions as an E3 SUMO1-p53 ligase. Fluorescence microscopy studies showed that E1B-55K alone, in the absence of other viral proteins, causes p53 to colocalize with E1B-55K in promyelocytic leukemia (PML) nuclear bodies, nuclear domains with a high concentration of sumoylated proteins. Photobleaching experiments with live cells revealed that E1B-55K tethering of p53 in PML nuclear bodies decreases the
in vivo
nuclear mobility of p53 nearly 2 orders of magnitude. E1B-55K-induced p53 sumoylation contributes to maximal inhibition of p53 function since mutation of the major p53 sumoylation site decreases E1B-55K-induced p53 sumoylation, tethering in PML nuclear bodies, and E1B-55K inhibition of p53 activity. Mutation of the E1B-55K sumoylation site greatly inhibits E1B-55K association with PML nuclear bodies and the p53 nuclear export to cytoplasmic aggresomes observed in E1A-E1B-transformed cells. Purified E1B-55K and p53 form high-molecular-weight complexes potentially through the formation of a network of E1B-55K dimers bound to the N termini of p53 tetramers. In support of this model, a p53 mutation that prevents tetramer formation greatly reduces E1B-55K-induced tethering in PML nuclear bodies and p53 nuclear export. These data indicate that E1B-55K's association with PML nuclear bodies inactivates p53 by first sequestering it in PML nuclear bodies and then greatly facilitating its nuclear export.
Cell-Cell Spread of Human Immunodeficiency Virus Type 1 Overcomes Tetherin/BST-2-Mediated Restriction in T cells
Authors: Jolly Clare , Booth Nicola J. , Neil Stuart J. D.
Published: September 2010

Direct cell-to-cell spread of human immunodeficiency virus type 1 (HIV-1) between T cells at the virological synapse (VS) is an efficient mechanism of viral dissemination. Tetherin (BST-2/CD317) is an interferon-induced, antiretroviral restriction factor that inhibits nascent cell-free particle release. The HIV-1 Vpu protein antagonizes tetherin activity; however, whether tetherin also restricts cell-cell spread is unclear. We performed quantitative cell-to-cell transfer analysis of wild-type (WT) or Vpu-defective HIV-1 in Jurkat and primary CD4
+
T cells, both of which express endogenous levels of tetherin. We found that Vpu-defective HIV-1 appeared to disseminate more efficiently by cell-to-cell contact between Jurkat cells under conditions where tetherin restricted cell-free virion release. In T cells infected with Vpu-defective HIV-1, tetherin was enriched at the VS, and VS formation was increased compared to the WT, correlating with an accumulation of virus envelope proteins on the cell surface. Increasing tetherin expression with type I interferon had only minor effects on cell-to-cell transmission. Furthermore, small interfering RNA (siRNA)-mediated depletion of tetherin decreased VS formation and cell-to-cell transmission of both Vpu-defective and WT HIV-1. Taken together, these data demonstrate that tetherin does not restrict VS-mediated T cell-to-T cell transfer of Vpu-defective HIV-1 and suggest that under some circumstances tetherin might promote cell-to-cell transfer, either by mediating the accumulation of virions on the cell surface or by regulating integrity of the VS. If so, inhibition of tetherin activity by Vpu may balance requirements for efficient cell-free virion production and cell-to-cell transfer of HIV-1 in the face of antiviral immune responses.
Induction of a Cross-Reactive CD8+T Cell Response following Foot-and-Mouth Disease Virus Vaccination
Authors: Guzman Efrain , Taylor Geraldine , Charleston Bryan , Ellis Shirley A.
Published: September 2010

Foot-and-mouth disease virus (FMDV) causes a highly contagious infection in cloven-hoofed animals. Current inactivated FMDV vaccines generate short-term, serotype-specific protection, mainly through neutralizing antibody. An improved understanding of the mechanisms of protective immunity would aid design of more effective vaccines. We have previously reported the presence of virus-specific CD8+T cells in FMDV-vaccinated and -infected cattle. In the current study, we aimed to identify CD8+T cell epitopes in FMDV recognized by cattle vaccinated with inactivated FMDV serotype O. Analysis of gamma interferon (IFN-γ)-producing CD8+T cells responding to stimulation with FMDV-derived peptides revealed one putative CD8+T cell epitope present within the structural protein P1D, comprising residues 795 to 803 of FMDV serotype O UKG/2001. The restricting major histocompatibility complex (MHC) class I allele was N*02201, expressed by the A31 haplotype. This epitope induced IFN-γ release, proliferation, and target cell killing by αβ CD8+T cells, but not CD4+T cells. A protein alignment of representative samples from each of the 7 FMDV serotypes showed that the putative epitope is highly conserved. CD8+T cells from FMDV serotype O-vaccinated A31+cattle recognized antigen-presenting cells (APCs) loaded with peptides derived from all 7 FMDV serotypes, suggesting that CD8+T cells recognizing the defined epitope are cross-reactive to equivalent peptides derived from all of the other FMDV serotypes.
A Double Mutation in Glycoprotein gB Compensates for Ineffective gD-Dependent Initiation of Herpes Simplex Virus Type 1 Infection
Authors: Uchida Hiroaki , Chan Janet , Goins William F. , Grandi Paola , Kumagai Izumi , Cohen Justus B. , Glorioso Joseph C.
Published: September 2010

Herpes simplex virus (HSV) entry into cells is triggered by the binding of envelope glycoprotein D (gD) to a specific receptor, such as nectin-1 or herpesvirus entry mediator (HVEM), resulting in activation of the fusion effectors gB and gH and virus penetration. Here we report the identification of a hyperactive gB allele, D285N/A549T, selected by repeat passage of a gD mutant virus defective for nectin-1 binding through cells that express a gD-binding-impaired mutant nectin-1. The gB allele in a wild-type virus background enabled the use of other nectins as virus entry receptors. In addition, combination of the mutant allele with an epidermal growth factor receptor (EGFR)-retargeted gD gene yielded dramatically increased EGFR-specific virus entry compared to retargeted virus carrying wild-type gB. Entry of the gB mutant virus into nectin-1-bearing cells was markedly accelerated compared to that of wild-type virus, suggesting that the gB mutations affect a rate-limiting step in entry. Our observations indicate that ineffective gD activation can be complemented by hypersensitization of a downstream component of the entry cascade to gD signaling.
ATR and ATRIP Are Recruited to Herpes Simplex Virus Type 1 Replication Compartments Even though ATR Signaling Is Disabled
Authors: Mohni Kareem N. , Livingston Christine M. , Cortez David , Weller Sandra K.
Published: September 2010

Although the herpes simplex virus type 1 (HSV-1) genome might be expected to induce a DNA damage response, the ATR kinase is not activated in infected cells. We previously proposed that spatial uncoupling of ATR from its interaction partner, ATRIP, could be the basis for inactivation of the ATR kinase in infected cells; however, we now show that ATR and ATRIP are in fact both recruited to HSV-1 replication compartments and can be coimmunoprecipitated from infected-cell lysates. ATRIP and replication protein A (RPA) are recruited to the earliest detectable prereplicative sites, stage II microfoci. In a normal cellular DNA damage response, ATR/ATRIP are recruited to stretches of RPA-coated single-stranded DNA in an RPA- and kinase-dependent manner, resulting in the phosphorylation of RPA by ATR in damage foci. In contrast, in HSV-1-infected cells, RPA is not phosphorylated, and endogenous phosphorylated RPA is excluded from stage II microfoci; in addition, the recruitment of ATR/ATRIP is independent of RPA and the kinase activity of ATR. Furthermore, we show that ATR/ATRIP play a beneficial role in viral gene expression and virus production. Although ICP0 has been shown to be important for partial inactivation of other cellular DNA repair pathways, we show that ICP0 is not responsible for the inactivation of ATR signaling and, furthermore, that neither ATR nor ATRIP is a target of ICP0 degradation. Thus, ATR and ATRIP may function outside the context of the canonical ATR damage signaling pathway during HSV-1 infection to participate in the viral life cycle.
The first metallacarborane triple-decker complexes with a bridging pentaphospholyl ligand
Authors: Loginov Dmitry A. , Vinogradov Mikhail M. , Starikova Zoya A. , Petrovskii Pavel V. , Holub Josef , Kudinov Alexander R.
Published: September 2010

Visible light irradiation of cations [(Carb)Fe(η-C6H6)]+ in the presence of Cp*Fe(η-cyclo-P5) affords the μ-pentaphospholyl triple-decker complexes [(Carb)Fe(μ-η:η-cyclo-P5)FeCp*]+ (Carb = 9-SMe2-7,8-C2B9H10 (3a) and 1-t-BuNH-1,7,9-C3B8H10 (3b)). Structures of 3a- and 3b[Co(η-7,8-C2B9H11)2] were determined by X-ray diffraction. Bonding in 3a, 3b and mononuclear building blocks was analyzed by energy decomposition analysis.
Practical management of the increasing burden of non-alcoholic fatty liver disease
Authors: Mouralidarane Angelina , Lin Ching-I , Suleyman Narin , Soeda Junpei , Oben Jude A
Published: September 2010

Obesity-induced liver disease (non-alcoholic fatty liver disease (NAFLD)) describes a spectrum from steatosis through steatohepatitis to cirrhosis. Its prevalence is rising in tandem with societal rates of obesity which through consequent insulin resistance and fat deposition in hepatocytes lead to hepatocyte death and attempts at repair, which if persistent, lead to activation of liver fibrogenic cells. NAFLD, which may also progress to primary liver cancer, is now the most common cause of chronic liver disease in affluent countries. There is currently no single accurate diagnostic test besides a liver biopsy. The decision to consider a liver biopsy will be informed by the presence of insulin resistance determined by comparatively easy-to-measure factors together with other putative markers of progression such as hypertension. If a liver biopsy is performed, patients with steatosis with no evidence of inflammation may be less aggressively managed while those with steatohepatitis, since they have a faster trajectory to cirrhosis, should be managed more robustly. Besides lifestyle changes and increased aerobic exercise other strategies include considering referral to centres with ongoing clinical trials. Emerging treatments include α1 adrenoceptors antagonists, angiotensin receptor blockers, glitazones and vitamin E.
The impact of smoking in Crohn's disease: no smoke without fire
Authors: Aldhous Marian C , Satsangi J
Published: September 2010

Smoking habit is the most widely accepted environmental factor affecting the incidence and disease progression in the inflammatory bowel diseases. The contrasting effects in Crohn's disease (CD) and ulcerative colitis are unexplained. The purpose of this review is to summarise the existing data on the effects of smoking in CD on disease history, recurrence after surgery, effects on drug responses and to review available evidence that carriage of some of the known susceptibility genes may be disproportionate in smokers with CD. The review also highlights potential mechanisms involved and factors that might affect patients' smoking habits. The clinical and scientific implications of the data are discussed.
Does constipation predict the quality of bowel preparation during colonoscopy?
Authors: Bloom Peter , Shustina Alexandra , Gaetano John N , Gualtieri Nicholas , Tievsky Dana , Robilotti James G
Published: September 2010

Background

Suboptimal bowel preparation has several consequences, including reduced polyp detection rate and increased cost of colorectal cancer screening. The presence of constipation is thought to be a feature associated with poor bowel preparation.

Objectives

To characterise the relationship between features of constipation and the quality of bowel preparation during colonoscopy.

Design

Patients presenting for an outpatient colonoscopy were asked to complete a questionnaire which included demographics, type of bowel purgative and features of bowel movements (BMs)—derived from the ROME III criteria for diagnosis of chronic constipation.

Patients

101 patients from the community undergoing surveillance colonoscopy completed the study.

Interventions

Patients underwent standard bowel preparation, completed a pre-endoscopy survey, followed by routine surveillance colonoscopy.

Main outcome measurements

The endoscopist rated the quality of bowel preparation using the previously validated Ottawa scoring scale. Statistical analysis was performed to characterise the relationship between the existence of chronic constipation and quality of bowel preparation.

Results

BM frequency of <1/day, 1/day, 2/day, or 3/day was inversely correlated with average total Ottawa score (range 5.93 to 4.00), p=0.028) as well as recto-sigmoid Ottawa score (range 1.8 to 1.0, p=0.006). Among women, there was a statistically significant (p=0.025) association between those who reported hard stools (Ottawa=6.3) and those who denied hard stools (4.5).

Conclusion

Eliciting features of BMs before colonoscopy may predict those at risk for poor bowel preparations and increase cost effectiveness of colonoscopy.
Why a PhD/MD enhances gastroenterological training: Figure 1
Authors: Farmer Adam D , Aziz Qasim
Published: September 2010

Academic medicine has faced an alarming decline in recent years necessitating the realisation of an integrated academic training pathway. This initiative has enabled many graduates to enter a structured academic training environment potentially leading to the award of a higher degree. A period of out of programme research or experience remains popular with trainees in gastroenterology, with up to 20% of trainees undertaking this at any one time. Most trainees believe that possessing a higher degree leads to improved job aspects. However, it is our belief that undertaking a higher degree leads to a global enhancement of gastroenterological training. Firstly, undertaking a higher degree facilitates the development of a myriad of personal and professional skills ranging from communication, research, scientific, critical thinking, problem solving to time and project management. These multifaceted transferrable skills are as applicable to the bedside as to the bench and in our belief are highly desirable with potential employers. Secondly, the acquisition of a higher degree allows the trainee to develop a subspecialty interest and a network of contacts, both national and international, within one's chosen field. Finally, we argue that the addition of time in research to the training period allows personal and professional maturation hitherto less easily achieved in the standard training period of 5 years. Overall, pursuing a higher degree in gastroenterology is a pursuit of excellence, something we should all strive for.
Bypassing the selection rule in choosing controls for a case–control study
Authors: Palmer Keith T , Kim Miranda , Coggon David
Published: September 2010

Objectives

It has been argued that in case–control studies, controls should be drawn from the base population that gives rise to the cases. In designing a study of occupational injury and risks arising from long-term illness and prescribed medication, we lacked data on subjects' occupation, without which employed cases (typically in manual occupations) would be compared with controls from the general population, including the unemployed and a higher proportion of white-collar professions. Collecting the missing data on occupation would be costly. We estimated the potential for bias if the selection rule were ignored.

Methods

We obtained published estimates of the frequencies of several exposures of interest (diabetes, mental health problems, asthma, coronary heart disease) in the general population, and of the relative risks of these diseases in unemployed versus employed individuals and in manual versus non-manual occupations. From these we computed the degree of over- or underestimation of exposure frequencies and exposure ORs if controls were selected from the general population.

Results

The potential bias in the OR was estimated as likely to fall between an underestimation of 14% and an overestimation of 36.7% (95th centiles). In fewer than 6% of simulations did the error exceed 30%, and in none did it reach 50%.

Conclusions

For the purposes of this study, in which we were interested only in substantial increases in risk, the potential for selection bias was judged acceptable. The rule that controls should come from the same base population as cases can justifiably be broken, at least in some circumstances.
Can exposure to a terrestrial trunked radio (TETRA)-like signal cause symptoms? A randomised double-blind provocation study
Authors: Nieto-Hernandez Rosa , Williams Jonathan , Cleare Anthony J , Landau Sabine , Wessely Simon , Rubin G James
Published: September 2010

Objectives

Concerns have been raised about possible health effects from radiofrequency fields pulsing at around 16 Hz. A radio system used by UK police (TETRA) employs signals which pulse at 17.6 Hz. We tested whether exposure to a continuous wave signal at 385.25 MHz or a TETRA-like signal resulted in symptoms among users reporting sensitivity to TETRA compared to users not reporting sensitivity to TETRA.

Methods

60 sensitive and 60 non-sensitive users were exposed to three 50 min conditions: a signal with a 16 Hz component, a continuous wave condition and a sham condition. The mean radiated power for the 16 Hz and continuous wave conditions was 250 mW. The order of conditions was randomised and testing was conducted double-blind. Participants reported the severity of eight symptoms during and after each exposure, their mood state at the end of each exposure, and whether they could tell which sessions involved active signals. The study was registered in advance with the ISRCTN register.

Results

Exposure to the continuous wave signal increased ratings of headache in all participants, fatigue in non-sensitive participants and difficulty concentrating in sensitive participants. Paradoxically, it reduced sensations of itching in sensitive participants. These effects were not observed in the condition with 16 Hz pulsing, except for those relating to concentration. Adjusting for multiple comparisons removed most significant effects, but not those relating to itch.

Conclusions

The results suggested that exposure to TETRA signals is not responsible for symptoms reported by some users, although exposure to a continuous wave signal may affect symptoms.

Clinical trial number

ISRCTN 73321766.
DYNAMICS OF A DISCRETE STOICHIOMETRIC TWO PREDATORS ONE PREY MODEL
Authors: XIE CONGBO , FAN MENG , ZHAO WEI
Published: September 2010

This paper derives a biologically reasonable discrete analog of a stoichiometric continuous two predators one prey model (i.e., LKEF model) proposed by Loladze et al.1By comparing the LKEF model to its discrete analog, we show that both the LKEF model and its discrete analogue exhibit similar dynamics but also some noticeable differences. In the discrete time setting, two predators exploiting a single prey can coexist not only at a stable equilibrium but also via oscillations, and the chaotic dynamics occur for biologically plausible parameter sets. Our results suggest that the stoichiometric mechanisms are robust to time discretization and the nutritional quality of prey has dramatic and counterintuitive impact on predator-prey dynamics, which agrees with the existing analysis of pelagic systems.
Soundscapes: Toward a Sounded Anthropology
Authors: Samuels David W. , Meintjes Louise , Ochoa Ana Maria , Porcello Thomas
Published: September 2010

A generation of scholars in multiple disciplines has investigated sound in ways that are productive for anthropologists. We introduce the concept of soundscape as a modality for integrating this work into an anthropological approach. We trace its history as a response to the technological mediations and listening practices emergent in modernity and note its absence in the anthropological literature. We then trace the history of technology that gave rise to anthropological recording practices, film sound techniques, and experimental sound art, noting productive interweavings of these threads. After considering ethnographies that explore relationships between sound, personhood, aesthetics, history, and ideology, we question sound's supposed ephemerality as a reason for the discipline's inattention. We conclude with a call for an anthropology that more seriously engages with its own history as a sounded discipline and moves forward in ways that incorporate the social and cultural sounded world more fully.
The Semiotics of Brand
Authors: Manning Paul
Published: September 2010

Approaches to the semiotics of brand are troubled by the lack of any accepted analytic definition of the phenomenon, as well as capacious, almost metaphysical, extensions in which brand becomes identified with semiosis as such, and thus everything is a brand. In addition, studies of brand tend to focus on highly visible or successful brands, as often as not as a proxy for a real object of analytic interest that lies elsewhere. Brand discourse defines brand in opposition to the material properties of the product, leading to a dematerialization of brand, which erases the messy materialities, contingencies, and hybrids that continually arise in the material semiosis of brand. Rather than attempt a definition of brand, the recent literature on brand semiotics is explored along several material and semiotic dimensions of the variousness of its relationship to its universes of circulation and in different professional discourses and historical and cultural contexts.